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Sökning: WFRF:(Hedman Åsa)

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1.
  • Axelsson, Mette, et al. (författare)
  • Mat vid diabetes. : En systematisk översikt med utvärdering av effekter samt hälsoekonomiska och etiska aspekter.
  • 2022
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • SlutsatserTyp 1- och typ 2-diabetes Det finns ett samband mellan att äta medelhavskost och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det finns ett samband mellan att äta en större andel2 fibrer eller baljväxter och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel nötter och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet) samt lägre risk att insjukna i hjärt- och kärlsjukdom (låg tillförlitlighet). Det finns ett samband mellan att dricka mer2 kaffe och lägre risk att dö i förtid oavsett orsak och lägre risk att dö i förtid i kranskärlssjukdom (måttlig tillförlitlighet) samt möjligen en lägre risk att dö i förtid i hjärt- och kärlsjukdom (låg tillförlitlighet). Det råder generell brist på studier med lång uppföljningstid som jämför inverkan av olika slags kostråd på överlevnad, diabeteskomplikationer, diabetesremission3, livskvalitet och biverkningar. Tillförlitligheten av befintliga resultat är dessutom mycket låg för de flesta koster, kostbehandlingar, livsmedel och näringsämnen som har utvärderats. Effekter på hälsa och relaterade mått kan i dessa fall inte bedömas.2. Begreppet ”större andel” eller ”mer” avser inte nödvändigtvis att äta eller dricka mer totalt utan att öka mängden av ett visst livsmedel genom att byta ut annan mat eller dryck.Typ 2-diabetes Det kan finnas ett samband mellan att äta en större andel mättat fett och högre risk för att dö i förtid av hjärt- och kärlsjukdom (låg tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel enkelomättat fett och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet). En behandling med en initial period av kraftigt minskat energiintag med hjälp av lågenergipulver (VLED) med efterföljande övergång till mat för viktstabilitet jämfört med vanlig kostbehandling har gynnsamma effekter på livskvalitet (enligt EQ-5D), långtidsblodsocker (HbA1c) och vikt upp till 12 månader (måttlig tillförlitlighet)4. Vidare kan metoder där VLED ingår ha gynnsamma effekter på diabetesremission5 och midjeomfång upp till 12 månader (låg tillförlitlighet) och långtidsblodsocker (HbA1c) upp till 24 månader (låg tillförlitlighet). Intensiv livsstilsbehandling därlågfettkost kombineras med fysisk aktivitet och minskat energiintag har gynnsamma effekter jämfört med vanlig kostbehandling på långtidsblodsocker (HbA1c), vikt, kroppsmasseindex (BMI), midjeomfång och vissa blodfetter upp till 12 månader (måttlig tillförlitlighet)3. Viktminskningen kan kvarstå upp till omkring 10 år (låg tillförlitlighet). Behandlingen kan leda till bättre fysisk livskvalitet upp till 8 år (låg tillförlitlighet) medan effektskillnaden i psykisk livskvalitet under samma tid kan vara obefintlig eller försumbar (låg tillförlitlighet). Jämförelsen påvisar ingen förändrad risk att dö i förtid oavsett orsak eller att dö eller insjukna av kardiovaskulära orsaker efter omkring 10 år (låg tillförlitlighet). I det hälsoekonomiska perspektivet är intensiv livsstilsbehandling mer resurskrävande än vanlig kostbehandling, och beräkningar visar små eller inga vinster i kvalitetsjusterade levnadsår (QALYs) på individnivå. Energirestriktion i samband med intensiv livsstilsbehandling med ketogen kost eller med högproteinkost (20 E%) i kombination med fysisk aktivitet jämfört med vanlig kostbehandling kan ge en viktminskning upp till 11 månader (låg tillförlitlighet) men det saknas studier som kan visa om vikten kan bibehållas på längre sikt. Det saknas studier som undersökt kliniskt viktiga utfall som dödlighet, kardiovaskulära sjukdomar, livskvalitet och diabetesremission.3. Gäller endast vid typ 2-diabetes.4. Utgår från individer med en medelkroppsvikt på cirka 100 kg och medel-HbA1c på 60 mmol/mol.5. Resultaten för utfallet diabetesremission (att uppnå normala blodsockervärden) gäller när en diabetesdiagnos sattes för mindre än 6 år sedan eller för mindre än 3 år sedan. Definitionen för diabetesremission var ett HbA1c på mindre än 48 mmol/mol och att samtidigt vara fri från blodsockersänkande läkemedel.Graviditetsdiabetes Det saknas studier om kost vid graviditetsdiabetes med tillräcklig tillförlitlighet för att kunna bedöma effekterna.
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2.
  • Ek, Weronica E, et al. (författare)
  • Genome-wide DNA methylation study identifies genes associated with the cardiovascular biomarker GDF-15
  • 2016
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:4, s. 817-827
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth-differentiation factor 15 (GDF-15) is expressed in low to moderate levels in most healthy tissues and increases in response to inflammation. GDF-15 is associated with cardiovascular dysfunction and over-expressed in the myocardium of patients with myocardial infarction (MI). However, little is known about the function of GDF-15 in cardiovascular disease, and the underlying regulatory network of GDF-15 is not known. To investigate a possible association between GDF-15 levels and DNA methylation, we performed a genome-wide DNA methylation study of white blood cells in a population-based study (N = 717). Significant loci where replicated in an independent cohort (N = 963). We also performed a gene ontology (GO) enrichment analysis. We identified and replicated 16 CpG-sites (false discovery rate [FDR] < 0.05), at 11 independent loci including MIR21. MIR21 encodes a microRNA (miR-21) that has previously been shown to be associated with the development of heart disease. Interestingly, GDF15 mRNA contains a binding site for miR-21. Four sites were also differentially methylated in blood from participants previously diagnosed with MI and 14 enriched GO terms (FDR < 0.05, enrichment > 2) were identified, including 'cardiac muscle cell differentiation'. This study shows that GDF-15 levels are associated with differences in DNA methylation in blood cells, and a subset of the loci are also differentially methylated in participants with MI. However, there might be interactions between GDF-15 levels and methylation in other tissues not addressed in this study. These results provide novel links between GDF-15 and cardiovascular disease.
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3.
  • Ek, Weronica E., et al. (författare)
  • Tea and coffee consumption in relation to DNA methylation in four European cohorts
  • 2017
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 26:16, s. 3221-3231
  • Tidskriftsartikel (refereegranskat)abstract
    • Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea has been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation.To investigate if DNA methylation in blood is associated with coffee and tea consumption we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed.After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated in men or in the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.
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4.
  • Folkersen, Lasse, et al. (författare)
  • Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
  • 2020
  • Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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5.
  • Klaric, Lucija, et al. (författare)
  • Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
  • 2021
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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6.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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7.
  • Allum, Fiona, et al. (författare)
  • Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants
  • 2015
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.
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8.
  • Anrup, Roland, et al. (författare)
  • Centrala universitetsvärden hotas av bolagiseringsidén
  • 2013
  • Ingår i: Dagens nyheter. - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Högskolestiftelser. Förslaget att driva svenska universitet i stiftelseform ­öppnar för bolagisering. Men det är ingen riktig utredning, utan en politisk pamflett utan ­eftertanke. Privatisering av universitet hotar både oberoendet, forskningskvaliteten och samhällsnyttan, skriver 36 forskare vid svenska högskolor och universitet.
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9.
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10.
  • Bjuhr, Åsa, 1973- (författare)
  • Avslut och fortsättning : En studie om övergången från introduktionsprogrammet språkintroduktion till nationellt program vid gymnasieskolan
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis highlights elements of the schooling for newly arrived students aged 16-19 within the Swedish school system in six different municipalities, where the transition between the language introduction programme and national programme at upper secondary school is central. The main purpose is to provide knowledge of pupils' experiences of the aforementioned transition. In this thesis, the concept of transition has a broader and more abstract meaning than just the actual move from one activity to another, and the thesis also focuses on the time spent in the language introduction programme and the first months in a national program at upper secondary school.Three studies are included in this thesis, where discourse analysis, curriculum theory and organizational theory of the school are used as a theoretical framework. The first study is an analysis of syllabuses from 1980 to 2011 for the subject Swedish as a second language within primary and secondary schools. The second is a study that interviews teachers in the language introduction programme, and the third study is based on interviews with pupils who have studied language introduction programme, but at the time of the interviews were studying in their first semester on a national programme.The analyses show that the transition is governed by curriculum and regulations that teachers and students must adhere to. The teachers carry out their everyday work on the basis of curriculum and regulations, such as the Education Act, but also on the basis of the individual school's organization. From an organizational perspective, this gives teachers limited personal room for manoeuvre. It also appears that the choice of national programmes and other choices that students can make within the framework of their schooling are sometimes obvious to the students and made by the students themselves. Nevertheless, other times teachers and study counsellors make the choices without the students’ knowledge. An additional result shows that the students say they experience a discrepancy when it comes to teaching of the various school subjects in the language introduction programme and the national programme at upper secondary school. The linguistic support that the students received during the time at the language introduction programme is not perceived by the students to be at the same level as the national programme. A development of linguistic support in various subjects within the national programme could, from a didactic perspective, lead to a less abrupt transition for the students
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11.
  • Carlsson Tedgren, Åsa, et al. (författare)
  • Response of LiF:Mg,Ti thermoluminescent dosimeters at photon energies relevant to the dosimetry of brachytherapy (andlt; 1 MeV)
  • 2011
  • Ingår i: Medical physics (Lancaster). - : American Association of Physicists in Medicine. - 0094-2405. ; 38:10, s. 5539-5550
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: High energy photon beams are used in calibrating dosimeters for use in brachytherapy since absorbed dose to water can be determined accurately and with traceability to primary standards in such beams, using calibrated ion chambers and standard dosimetry protocols. For use in brachytherapy, beam quality correction factors are needed, which include corrections for differences in mass energy absorption properties between water and detector as well as variations in detector response (intrinsic efficiency) with radiation quality, caused by variations in the density of ionization (linear energy transfer (LET) -distributions) along the secondary electron tracks. The aim of this work was to investigate experimentally the detector response of LiF:Mg, Ti thermoluminescent dosimeters (TLD) for photon energies below 1 MeV relative to (60)Co and to address discrepancies between the results found in recent publications of detector response. less thanbrgreater than less thanbrgreater thanMethods: LiF:Mg,Ti dosimeters of formulation MTS-N Poland were irradiated to known values of air kerma free-in-air in x-ray beams at tube voltages 25-250 kV, in (137)Cs- and (60)Co-beams at the Swedish Secondary Standards Dosimetry Laboratory. Conversions from air kerma free-in-air into values of mean absorbed dose in the dosimeters in the actual irradiation geometries were made using EGSnrc Monte Carlo simulations. X-ray energy spectra were measured or calculated for the actual beams. Detector response relative to that for (60)Co was determined at each beam quality. less thanbrgreater than less thanbrgreater thanResults: An increase in relative response was seen for all beam qualities ranging from 8% at tube voltage 25 kV (effective energy 13 keV) to 3%-4% at 250 kV (122 keV effective energy) and (137)Cs with a minimum at 80 keV effective energy (tube voltage 180 kV). The variation with effective energy was similar to that reported by Davis [Radiat. Prot. Dosim. 106, 33-43 (2003)] with our values being systematically lower by 2%-4%. Compared to the results by Nunn [Med. Phys. 35, 1861-1869 (2008)], the relative detector response as a function of effective energy differed in both shape and magnitude. This could be explained by the higher maximum read-out temperature (350 degrees C) used by Nunn [Med. Phys. 35, 1861-1869 (2008)], allowing light emitted from high-temperature peaks with a strong LET dependence to be registered. Use of TLD-100 by Davis [Radiat. Prot. Dosim. 106, 33-43 (2003)] with a stronger super-linear dose response compared to MTS-N was identified as causing the lower relative detector response in this work. less thanbrgreater than less thanbrgreater thanConclusions: Both careful dosimetry and strict protocols for handling the TLDs are required to reach solid experimental data on relative detector response. This work confirms older findings that an over-response relative to (60)Co exists for photon energies below 200-300 keV. Comparison with the results from the literature indicates that using similar protocols for annealing and read-out, dosimeters of different makes (TLD-100, MTS-N) differ in relative detector response. Though universality of the results has not been proven and further investigation is needed, it is anticipated that with the use of strict protocols for annealing and read-out, it will be possible to determine correction factors that can be used to reduce uncertainties in dose measurements around brachytherapy sources at photon energies where primary standards for absorbed dose to water are not available.
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12.
  • Cho, Yoon Shin, et al. (författare)
  • Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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13.
  • Demerath, Ellen W., et al. (författare)
  • Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci
  • 2015
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:15, s. 4464-4479
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed-effects regression models were used to test the association of methylation beta value with concurrent body mass index (BMI) and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole-blood DNA from 2377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the Genetics of Lipid Lowering Drugs and Diet Network Study was followed by testing using adipose tissue DNA from 648 women in the Multiple Tissue Human Expression Resource cohort. Seventy-six BMI-related probes, 164 WC-related probes and 8 BMI change-related probes passed the threshold for significance in ARIC (P < 1 x 10(-7); Bonferroni), including probes in the recently reported HIF3A, CPT1A and ABCG1 regions. Replication using blood DNA was achieved for 37 BMI probes and 1 additional WC probe. Sixteen of these also replicated in adipose tissue, including 15 novel methylation findings near genes involved in lipid metabolism, immune response/cytokine signaling and other diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity and analytic approaches.
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14.
  • Drong, Alexander W, et al. (författare)
  • The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue.
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants that associate with DNA methylation at CpG sites (methylation quantitative trait loci, meQTLs) offer a potential biological mechanism of action for disease associated SNPs. We investigated whether meQTLs exist in abdominal subcutaneous adipose tissue (SAT) and if CpG methylation associates with metabolic syndrome (MetSyn) phenotypes. We profiled 27,718 genomic regions in abdominal SAT samples of 38 unrelated individuals using differential methylation hybridization (DMH) together with genotypes at 5,227,243 SNPs and expression of 17,209 mRNA transcripts. Validation and replication of significant meQTLs was pursued in an independent cohort of 181 female twins. We find that, at 5% false discovery rate, methylation levels of 149 DMH regions associate with at least one SNP in a ±500 kilobase cis-region in our primary study. We sought to validate 19 of these in the replication study and find that five of these significantly associate with the corresponding meQTL SNPs from the primary study. We find that none of the 149 meQTL top SNPs is a significant expression quantitative trait locus in our expression data, but we observed association between expression levels of two mRNA transcripts and cis-methylation status. Our results indicate that DNA CpG methylation in abdominal SAT is partly under genetic control. This study provides a starting point for future investigations of DNA methylation in adipose tissue.
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15.
  • Flerspråkighet, litteracitet och multimodalitet
  • 2013
  • Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
    • Många människor, såväl barn som tonåringar och vuxna, lever i flerspråkiga sammanhang som skiljer sig väsentligt från den enspråkiga miljö som ofta tas för given i skola och vuxenutbildning. Där har man i stället många gånger haft svårt att förhålla sig till flerspråkighet och ofta utgått ifrån ett bristperspektiv. Detta gäller inte minst skriftspråksundervisningen, där elevernas egna erfarenheter av en flexibel flerspråkighet utanför klassrummet alltför sällan tas tillvara.I den här antologin presenterar ett antal forskare exempel på skriftspråkliga erfarenheter, både flerspråkiga och multimodala, som sällan uppmärksammas i skolan. I sina studier har de sett en mängd goda exempel på hur lärare arbetar i klassrummet för att gynna skriftspråksutvecklingen hos flerspråkiga elever – deras multilitteracitet. En sådan medvetenhet hos läraren kan t.ex. handla om alltifrån att ha kunskap om effektiva läsförståelsestrategier till att förstå hur multimodalitet i läroböcker och multimodalt textskapande i klassrummet stärker lärande och flerspråkig kompetens.Boken vänder sig främst till blivande och verksamma lärare i skola och vuxenutbildning.
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16.
  • Ganna, Andrea, et al. (författare)
  • Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease
  • 2014
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 10:12, s. e1004801-
  • Tidskriftsartikel (refereegranskat)abstract
    • Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.
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17.
  • Glass, Daniel, et al. (författare)
  • Gene expression changes with age in skin, adipose tissue, blood and brain.
  • 2013
  • Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 14:7
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age.RESULTS: Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues.CONCLUSIONS: Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.
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18.
  • Grundberg, Elin, et al. (författare)
  • Mapping cis- and trans-regulatory effects across multiple tissues in twins.
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. Using identity-by-descent estimates, we show that at least 40% of the total heritable cis effect on expression cannot be accounted for by common cis variants, a finding that reveals the contribution of low-frequency and rare regulatory variants with respect to both transcriptional regulation and complex trait susceptibility. We show that a substantial proportion of gene expression heritability is trans to the structural gene, and we identify several replicating trans variants that act predominantly in a tissue-restricted manner and may regulate the transcription of many genes.
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19.
  • Hansson, Oskar, et al. (författare)
  • The genetic regulation of protein expression in cerebrospinal fluid
  • 2023
  • Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of the genetic regulation of cerebrospinal fluid (CSF) proteins may reveal pathways for treatment of neurological diseases. 398 proteins in CSF were measured in 1,591 participants from the BioFINDER study. Protein quantitative trait loci (pQTL) were identified as associations between genetic variants and proteins, with 176 pQTLs for 145 CSF proteins (P < 1.25 × 10−10, 117 cis-pQTLs and 59 trans-pQTLs). Ventricular volume (measured with brain magnetic resonance imaging) was a confounder for several pQTLs. pQTLs for CSF and plasma proteins were overall correlated, but CSF-specific pQTLs were also observed. Mendelian randomization analyses suggested causal roles for several proteins, for example, ApoE, CD33, and GRN in Alzheimer's disease, MMP-10 in preclinical Alzheimer's disease, SIGLEC9 in amyotrophic lateral sclerosis, and CD38, GPNMB, and ADAM15 in Parkinson's disease. CSF levels of GRN, MMP-10, and GPNMB were altered in Alzheimer's disease, preclinical Alzheimer's disease, and Parkinson's disease, respectively. These findings point to pathways to be explored for novel therapies. The novel finding that ventricular volume confounded pQTLs has implications for design of future studies of the genetic regulation of the CSF proteome.
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20.
  • Hedman, Linnea, 1979-, et al. (författare)
  • Diagnostic intervention improved health-related quality of life among teenagers with food allergy
  • 2024
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:1 January
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives:  The aim was to examine if a diagnostic intervention set up to assess current food allergy to cow’s milk, hen’s egg, fish, or wheat among teenagers had an impact on generic and disease specific health-related quality of life (HRQL). The study compared HRQL scoring before and two years after the intervention, and in relation to age matched controls without reported food allergy.Methods: The study was performed within the Obstructive Lung Disease in Northern Sweden (OLIN) studies where a cohort study on asthma and allergic diseases among 8-year-old schoolchildren was initiated in 2006. At age 12 years, the 125/2612 (5%) children who reported allergy to cow’s milk, hen’s egg, fish, or wheat were invited to a diagnostic intervention including clinical examination, blood tests and evaluation by a pediatric allergist. Of 94 participants, 79 completed generic and disease specific HRQL questionnaires. Additionally, a random sample of 200 (62% of invited) children without food allergy from the OLIN cohort answered the generic HRQL questionnaire. The respondents of the HRQL questionnaires were reexamined two years later and 57 teenagers with and 154 without reported allergy participated.Results: There were no significant differences in generic HRQL scores between teenagers with and without reported food allergy at study entry, or after the intervention. Among those with reported food allergy, we found a significant improvement in disease specific HRQL after the intervention (mean values: 3.41 vs 2.80, p<0.001). Teenagers with only food allergy had better disease specific HRQL compared to those with one, two or three concomitant allergic diseases, both before and after the intervention. Children with only food allergy significantly improved their HRQL after the intervention, 1.84 vs. 2.87 (p<0.001) but this association was not seen in children with one other allergic disorder (3.16 vs. 3.65, p = 0.121) or those with two or more allergic disorders (3.72 vs. 3.90, p = 0.148).Conclusion: The diagnostic intervention showed a long-term improvement of disease specific HRQL but not generic HRQL.
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21.
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22.
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23.
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24.
  • Hedman, Åsa-Helena, et al. (författare)
  • Thai-Swedish couples in the Swedish daily press-discursive constitutions of 'The Other'
  • 2009
  • Ingår i: NORA. - : Routledge. - 0803-8740 .- 1502-394X. ; 17:1, s. 34-47
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examines discursive representations of Thai-Swedish couples in the Swedish daily press. The sample studied includes 17 articles. The study shows that the couples are constituted as inherently “different” through interweaving discourses such as a romantic love discourse, a sex tourism discourse, and a normalizing discourse, and through intersecting power relations such as those of gender, “race”/ethnicity, class, and sexuality. The normalized position representing “Swedishness” is not usually made explicit but is nevertheless constantly reproduced, and hierarchies are formed within as well as between the “normal” couple and “the Other”
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25.
  • Hedman, Åsa, et al. (författare)
  • IEA EBC Annex83 Positive Energy Districts
  • 2021
  • Ingår i: Buildings. - : MDPI AG. - 2075-5309. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • At a global level, the need for energy efficiency and an increased share of renewable energy sources is evident, as is the crucial role of cities due to the rapid urbanization rate. As a consequence of this, the research work related to Positive Energy Districts (PED) has accelerated in recent years. A common shared definition, as well as technological approaches or methodological issues related to PEDs are still unclear in this development and a global scientific discussion is needed. The International Energy Agency’s Energy in Buildings and Communities Programme (IEA EBC) Annex 83 is the main platform for this international scientific debate and research. This paper describes the challenges of PEDs and the issues that are open for discussions and how the Annex 83 is planned and organized to facilitate this and to actively steer the development of PEDs major leaps forward. The main topics of discussion in the PED context are the role and importance of definitions of PEDs, virtual and geographical boundaries in PEDs, the role of different stakeholders, evaluation approaches, and the learnings of realized PED projects.
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26.
  • Hedman, Åsa K., et al. (författare)
  • DNA methylation patterns associated with oxidative stress in an ageing population
  • 2016
  • Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Oxidative stress has been related to type 2 diabetes (T2D) and cardiovascular disease (CVD), the leading global cause of death. Contributions of environmental factors such as oxidative stress on complex traits and disease may be partly mediated through changes in epigenetic marks (e.g. DNA methylation). Studies relating differential methylation with intermediate phenotypes and disease endpoints may be useful in identifying additional candidate genes and mechanisms involved in disease. Methods: To investigate the role of epigenetic variation in oxidative stress marker levels and subsequent development of CVD and T2D, we performed analyses of genome-wide DNA methylation in blood, ten markers of oxidative stress (total glutathione [TGSH], reduced glutathione [GSH], oxidised glutathione [GSSG], GSSG to GSH ratio, homocysteine [HCY], oxidised low-density lipoprotein (oxLDL), antibodies against oxLDL [OLAB], conjugated dienes [CD], baseline conjugated dienes [BCD]-LDL and total antioxidant capacity [TAOC]) and incident disease in up to 966 age-matched individuals. Results: In total, we found 66 cytosine-guanine (CpG) sites associated with one or more oxidative stress markers (false discovery rate [FDR] <0.05). These sites were enriched in regulatory regions of the genome. Genes annotated to CpG sites showed enrichment in annotation clusters relating to phospho-metabolism and proteins with pleckstrin domains. We investigated the contribution of oxidative stress-associated CpGs to development of cardiometabolic disease. Methylation variation at CpGs in the 3'-UTR of HIST1H4D (cg08170869; histone cluster 1, H4d) and in the body of DVL1 (cg03465880; dishevelled-1) were associated with incident T2D events during 10 years of follow-up (all permutation p-values < 0.01), indicating a role of epigenetic regulation in oxidative stress processes leading to development or progression of diabetes. Methylation QTL (meQTL) analysis showed significant associations with genetic sequence variants in cis at 28 (42%) of oxidative stress phenotype-associated sites (FDR < 0.05). Integrating cis-meQTLs with genotype-phenotype associations indicated that genetic effects on oxidative stress phenotype at one locus (cg07547695; BCL2L11) may be mediated through DNA methylation. Conclusions: In conclusion, we report novel associations of DNA methylation with oxidative stress, some of which also show evidence of a relation with T2D incidence.
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27.
  • Hedman, Åsa K., et al. (författare)
  • Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies
  • 2017
  • Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background- Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. Methods and Results- To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage (P < 1.08E-07) and replicated 33 (at Bonferroni-corrected P < 0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglyceridesand high-density lipoprotein cholesterol (HDL- C; cg27243685; P= 8.1E-26 and 9.3E-19) was associated with cis-expression of a reverse cholesterol transporter (ABCG1; P= 7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P= 0.0007). We found significant cis-methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels (P-TC = 0.004, PHDL-C = 0.008 and P-triglycerides = 0.00003) and coronary heart disease ( P= 0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis-methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. Conclusions-We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events.
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28.
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29.
  • Jhun, Mina-A, et al. (författare)
  • A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids
  • 2021
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups. Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.
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30.
  • Johansson, Åsa, et al. (författare)
  • Precision medicine in complex diseases - : Molecular subgrouping for improved prediction and treatment stratification
  • 2023
  • Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 1365-2796 .- 0954-6820. ; 294:4, s. 378-396
  • Forskningsöversikt (refereegranskat)abstract
    • Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.
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31.
  • Jonsson, Lisa, et al. (författare)
  • Att lära genom att skriva : effekter på elevers ämneskunskaper i NO, SO och matematik
  • 2022
  • Rapport (populärvet., debatt m.m.)abstract
    • I rapporten sammanfattas och kommenteras en internationell forskningsöversikt som visar att skrivande förbättrar elevers ämneskunskaper i NO, SO och matematik, jämfört med undervisning som har mindre fokus på skrivande. Rapporten består dels av en sammanfattning av forskningsöversiktens utgångspunkter, metod och resultat, dels av en kommentar till resultaten utifrån ett svenskt sammanhang. I kommentaren diskuteras även sådant som kan vara bra att tänka på när man som lärare använder skrivande för att förbättra elevers ämneskunskaper.
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32.
  • Keildson, Sarah, et al. (författare)
  • Expression of phosphofructokinase in skeletal muscle is influenced by genetic variation and associated with insulin sensitivity.
  • 2014
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Using an integrative approach in which genetic variation, gene expression, and clinical phenotypes are assessed in relevant tissues may help functionally characterize the contribution of genetics to disease susceptibility. We sought to identify genetic variation influencing skeletal muscle gene expression (expression quantitative trait loci [eQTLs]) as well as expression associated with measures of insulin sensitivity. We investigated associations of 3,799,401 genetic variants in expression of >7,000 genes from three cohorts (n = 104). We identified 287 genes with cis-acting eQTLs (false discovery rate [FDR] <5%; P < 1.96 × 10(-5)) and 49 expression-insulin sensitivity phenotype associations (i.e., fasting insulin, homeostasis model assessment-insulin resistance, and BMI) (FDR <5%; P = 1.34 × 10(-4)). One of these associations, fasting insulin/phosphofructokinase (PFKM), overlaps with an eQTL. Furthermore, the expression of PFKM, a rate-limiting enzyme in glycolysis, was nominally associated with glucose uptake in skeletal muscle (P = 0.026; n = 42) and overexpressed (Bonferroni-corrected P = 0.03) in skeletal muscle of patients with T2D (n = 102) compared with normoglycemic controls (n = 87). The PFKM eQTL (rs4547172; P = 7.69 × 10(-6)) was nominally associated with glucose uptake, glucose oxidation rate, intramuscular triglyceride content, and metabolic flexibility (P = 0.016-0.048; n = 178). We explored eQTL results using published data from genome-wide association studies (DIAGRAM and MAGIC), and a proxy for the PFKM eQTL (rs11168327; r(2) = 0.75) was nominally associated with T2D (DIAGRAM P = 2.7 × 10(-3)). Taken together, our analysis highlights PFKM as a potential regulator of skeletal muscle insulin sensitivity.
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33.
  • Kilpeläinen, Tuomas O, et al. (författare)
  • Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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34.
  • Leffler, Eva, 1956- (författare)
  • Företagsamma elever : Diskurser kring entreprenörskap och företagsamhet i skolan
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this thesis is to study and problematize the concepts of entrepreneurship and enterprise in Swed-ish compulsory schools. The studies presented in this thesis focus both on scientific publications and official documents that deal with entrepreneurship and enterprise in compulsory schools and on school projects that have been carried out in years 4 to 6 in the county of Västerbotten. The main questions of the study are: • How did the discourse on entrepreneurship and enterprise in school arise? • What do concepts of entrepreneurship and enterprise mean in Swedish nine-year compulsory schools? • How is discursive practice concerning Entrepreneurship and Enterprise in schools expressed? Michel Foucault’s theories of discourse, power and discipline have been used as analytical tools, together with gender theories. Characteristic for the research on entrepreneurship is that it is multidisciplinary. There are difficulties, both nationally and internationally, to explicitly define the concept of ”entrepreneur”. The entrepreneur is described as an individual with abilities to take action, initiative and risks but also as being creative, innovative and cooperative. These are characteristics that both society and school can make use of. Unemployment among young people and changing needs in society are reasons why the concept “enter-prise” is present on most of the agendas of the OECD countries today. Society requires individuals who can take responsibility and initiative and who are creative. Training in and about entrepreneurship has devel-oped and therefore it has been possible to stress its relevance for the entire educational system. Training for entrepreneurship is directed towards economics, i e a discourse about enterprise while training about entre-preneurship turns against training in general by relating to up-bringing and human inner qualities. A dis-course in enterprise has been formed, whose aim is to develop pupils into responsible, creative, active, cooperative and enterprising members of society. This is where a new discourse is created and it is a dis-course in enterprise and schools. Even so, the road into school is via economics because the main aim of entrepreneurship is economic growth and increased employment rate. Throughout the different texts about entrepreneurship and enterprise in school there is a tendency to use dichotomies. In this case it concerns what is the right or the wrong way of teaching. Enterprise teaching, as it is used in entrepreneurship and enterprise in schools, is considered the right and true way of teaching, while the practice in schools is de-scribed as the opposite. A struggle between two discourses appears; the struggle between the entrepreneurial school discourse and the official school discourse, the latter with its origin in the national curriculum from 1994, Lpo 94. At the end of the 1990s a number of school projects were initiated, both nationally and inter-nationally, aiming at stimulating pupils’ enterprising skills. In the county of Västerbotten school projects were initiated under the overarching project PRIO1, Priority Enterprise County of Västerbotten and in-cluded students of all ages. The schools could choose either an entrepreneurial or an enterprising approach to their projects. The enterprise approach was more invisible, less concrete and more difficult to evaluate and measure. The work with entrepreneurship and enterprise in school in the investigated schools show that well-established and current discourses in the schools were transferred to the ”new” discourse. Instead of transferring the “new aspects” that the project was expected to contribute to the current discourse, the ”old” and already well-known aspects were transferred to the new discourse. Consequently, the projects themselves did not result in a comprehensive change of the discourse in practice.
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35.
  • Liu, C, et al. (författare)
  • A DNA methylation biomarker of alcohol consumption.
  • 2018
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23, s. 422-433
  • Tidskriftsartikel (refereegranskat)abstract
    • The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.
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36.
  • Love-Gregory, Latisha, et al. (författare)
  • Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36
  • 2016
  • Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 57:12, s. 2176-2184
  • Tidskriftsartikel (refereegranskat)abstract
    • Cluster of differentiation 36 (CD36) variants influence fasting lipids and risk of metabolic syndrome, but their impact on postprandial lipids, an independent risk factor for cardiovascular disease, is unclear. We determined the effects of SNPs within a approximate to 410 kb region encompassing CD36 and its proximal and distal promoters on chylomicron (CM) remnants and LDL particles at fasting and at 3.5 and 6 h following a high-fat meal (Genetics of Lipid Lowering Drugs and Diet Network study, n = 1,117). Five promoter variants associated with CMs, four with delayed TG clearance and five with LDL particle number. To assess mechanisms underlying the associations, we queried expression quantitative trait loci, DNA methylation, and ChIP-seq datasets for adipose and heart tissues that function in postprandial lipid clearance. Several SNPs that associated with higher serum lipids correlated with lower adipose and heart CD36 mRNA and aligned to active motifs for PPAR, a major CD36 regulator. The SNPs also associated with DNA methylation sites that related to reduced CD36 mRNA and higher serum lipids, but mixed-model analyses indicated that the SNPs and methylation independently influence CD36 mRNA. The findings support contributions of CD36 SNPs that reduce adipose and heart CD36 RNA expression to inter-individual variability of postprandial lipid metabolism and document changes in CD36 DNA methylation that influence both CD36 expression and lipids.
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37.
  • Lu, Yingchang, et al. (författare)
  • New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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38.
  • Mendelson, Michael M., et al. (författare)
  • Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease : A Mendelian Randomization Approach
  • 2017
  • Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.
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39.
  • Mälarstig, Anders, et al. (författare)
  • Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.
  •  
40.
  • Parts, Leopold, et al. (författare)
  • Extent, causes, and consequences of small RNA expression variation in human adipose tissue.
  • 2012
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Small RNAs are functional molecules that modulate mRNA transcripts and have been implicated in the aetiology of several common diseases. However, little is known about the extent of their variability within the human population. Here, we characterise the extent, causes, and effects of naturally occurring variation in expression and sequence of small RNAs from adipose tissue in relation to genotype, gene expression, and metabolic traits in the MuTHER reference cohort. We profiled the expression of 15 to 30 base pair RNA molecules in subcutaneous adipose tissue from 131 individuals using high-throughput sequencing, and quantified levels of 591 microRNAs and small nucleolar RNAs. We identified three genetic variants and three RNA editing events. Highly expressed small RNAs are more conserved within mammals than average, as are those with highly variable expression. We identified 14 genetic loci significantly associated with nearby small RNA expression levels, seven of which also regulate an mRNA transcript level in the same region. In addition, these loci are enriched for variants significant in genome-wide association studies for body mass index. Contrary to expectation, we found no evidence for negative correlation between expression level of a microRNA and its target mRNAs. Trunk fat mass, body mass index, and fasting insulin were associated with more than twenty small RNA expression levels each, while fasting glucose had no significant associations. This study highlights the similar genetic complexity and shared genetic control of small RNA and mRNA transcripts, and gives a quantitative picture of small RNA expression variation in the human population.
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41.
  • Pfeiffer, Liliane, et al. (författare)
  • DNA methylation of lipid-related genes affects blood lipid levels.
  • 2015
  • Ingår i: Circulation. - 1942-325X .- 1942-3268. ; 8:2, s. 334-42
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Epigenetic mechanisms might be involved in the regulation of interindividual lipid level variability and thus may contribute to the cardiovascular risk profile. The aim of this study was to investigate the association between genome-wide DNA methylation and blood lipid levels high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. Observed DNA methylation changes were also further analyzed to examine their relationship with previous hospitalized myocardial infarction.METHODS AND RESULTS: Genome-wide DNA methylation patterns were determined in whole blood samples of 1776 subjects of the Cooperative Health Research in the Region of Augsburg F4 cohort using the Infinium HumanMethylation450 BeadChip (Illumina). Ten novel lipid-related CpG sites annotated to various genes including ABCG1, MIR33B/SREBF1, and TNIP1 were identified. CpG cg06500161, located in ABCG1, was associated in opposite directions with both high-density lipoprotein cholesterol (β coefficient=-0.049; P=8.26E-17) and triglyceride levels (β=0.070; P=1.21E-27). Eight associations were confirmed by replication in the Cooperative Health Research in the Region of Augsburg F3 study (n=499) and in the Invecchiare in Chianti, Aging in the Chianti Area study (n=472). Associations between triglyceride levels and SREBF1 and ABCG1 were also found in adipose tissue of the Multiple Tissue Human Expression Resource cohort (n=634). Expression analysis revealed an association between ABCG1 methylation and lipid levels that might be partly mediated by ABCG1 expression. DNA methylation of ABCG1 might also play a role in previous hospitalized myocardial infarction (odds ratio, 1.15; 95% confidence interval=1.06-1.25).CONCLUSIONS: Epigenetic modifications of the newly identified loci might regulate disturbed blood lipid levels and thus contribute to the development of complex lipid-related diseases.
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42.
  • Price, Thomas S, et al. (författare)
  • SW-ARRAY : a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data.
  • 2005
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 33:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array CGH studies of the human genome noting false negative and false positive results using large insert clones as probes have raised important concerns regarding the suitability of this approach for clinical diagnostic applications. Here, we adapt the Smith-Waterman dynamic-programming algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for detecting copy-number changes in array CGH data. In a blind series of hybridizations to arrays consisting of the entire tiling path for the terminal 2 Mb of human chromosome 16p, the method identified all monosomies between 267 and 1567 kb with a high degree of statistical significance and accurately located the boundaries of deletions in the range 267-1052 kb. The approach is unique in offering both a nonparametric segmentation procedure and a nonparametric test of significance. It is scalable and well-suited to high resolution whole genome array CGH studies that use array probes derived from large insert clones as well as PCR products and oligonucleotides.
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43.
  • Rahmioglu, Nilufer, et al. (författare)
  • Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci
  • 2015
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:4, s. 1185-1199
  • Tidskriftsartikel (refereegranskat)abstract
    • Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other.
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44.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
  •  
45.
  • Small, K. S., et al. (författare)
  • Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes
  • 2011
  • Ingår i: Nat Genet. ; 43:6, s. 561-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have identified many genetic variants associated with complex traits. However, at only a minority of loci have the molecular mechanisms mediating these associations been characterized. In parallel, whereas cis regulatory patterns of gene expression have been extensively explored, the identification of trans regulatory effects in humans has attracted less attention. Here we show that the type 2 diabetes and high-density lipoprotein cholesterol-associated cis-acting expression quantitative trait locus (eQTL) of the maternally expressed transcription factor KLF14 acts as a master trans regulator of adipose gene expression. Expression levels of genes regulated by this trans-eQTL are highly correlated with concurrently measured metabolic traits, and a subset of the trans-regulated genes harbor variants directly associated with metabolic phenotypes. This trans-eQTL network provides a mechanistic understanding of the effect of the KLF14 locus on metabolic disease risk and offers a potential model for other complex traits.
  •  
46.
  • Smith-Byrne, Karl, et al. (författare)
  • Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
  • 2024
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalization. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.
  •  
47.
  • Stibrant Sunnerhagen, Katharina, 1957, et al. (författare)
  • Rehabilitation after cardiac arrest
  • 2014
  • Ingår i: World Congress of Neuro Rehabilitation Istanbul, Turkiet 8-12 april 2014.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Cardiac arrest (CA) is a life-threatening condition. In the last decade there has been an increase in survival after out-of-hospital cardiac arrest and in 2011, about 500 patients survived an OHCA in Sweden, measured as 30-day survival. Brain damage depend on level oxygen deprivation as well length of impaired circulation. Common symptoms include difficulties with short-term memory, learning tasks and motor deficits. Aims To describe the results of rehabilitation of CA survivors. Material and methods Between 2007 and 2011, 150 patients with anoxic brain injury after CA received in-patient rehabilitation in different clinics in Sweden and reported to the quality register WebRehab. The average age was 48.6 years (SD 15.4, range 15-82 years) and there were 64 women and 86 men. Time from CA tol admittance was 24 days (SD 28.8). Dependency was assessed by FIM, and defined as motor FIM (13x6-1) and social-cognitive FIM (5x6-1); i.e. dependence in at least 1 item. Wilcoxon signed test was used to assess significant changes in dependence. Results At admittance, 74 % were dependent in motor FIM and 47 % in social-cognitive FIM. 46% were wheel-chair users. Length of stay was 68 days (SD 60). During the rehabilitation period the motor function increased significantly (p<0.05) with 42 % dependent in motor FIM and 30 % were still wheel-chair users. Little change occurred in social-cognitive FIM, where still 42 % were dependent at discharge, 33% went home without any need for support, 40 % went to their own home with support from the community and 14% to nursing homes and 13 % to another hospital ward. Conclusion Motor functions seem to recover better than cognitive functions after CA. Even with more than 2 months of in-patient rehab, little improvement is noted in social-cognitive FIM. Those CA survivors that need rehabilitation, often remain dependent on others for the rest of their lives.
  •  
48.
  • Stibrant Sunnerhagen, Katharina, 1957, et al. (författare)
  • Rehabilitation After Tick Born Encephalitis
  • 2014
  • Ingår i: World Congress of Neuro Rehabilitation Istanbul, Turkiet 8-12 april 2014.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Tick born encephalitis (TBE) is a zoonosis, transmitted through ticks. Every year around 150–200 cases of TBE are reported in Sweden. TBE is also seen in Finland, the Baltic States and in middle Europe and increasing in frequuency. The disease is most often manifest as meningitis or encephalitis. Long-lasting or permanent neuropsychiatric sequel has been reported in 10-20% of infected patients. A structured analysis of the trajectory is missing and the rehabilitation course of TBE patients has not been reported. Aims To explore the consequences of TBE for rehab Material and methods 32 patients were admitted to the different rehabilitation clinics in Sweden and 16 men and 16 women and reported to the Swedish quality register Web Rehab during a 5 year period. The average age was 47 years (SD 12.6). Time from diagnosis until admittance for rehab was 29 days (SD 21.8). Dependency was assessed by FIM, and defined as motor FIM (13x6-1) and social-cognitive FIM (5x6-1); i.e. dependence in at least 1 item. Wilcoxon signed test was used to assess significant changes in dependence. Results At admittance, half were dependent in motor FIM and 47 % in social-cognitive FIM. Length of stay was 41 days (SD 26.8). During the rehabilitation period there was a significant improvement in motor FIM (p=0.003) and social-cognitive FIM (p=0.025). The majority was discharged to home without any need for support (22), 7 to their own home but with support from the community and 3 to nursing homes. Conclusion The number of patients (32) admitted for in-patient rehab is lower than one would expect if the report of 10-20 % with sequels is correct. Either the level of sequels is lower than thought or the patients not referred. The frequency of dependency in those admitted is only around 50 %. The majority are discharged to an independent life. These positive results need to be deeper explored since subtle cognitive problems might be missed in ADL activities.
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49.
  • Strinnholm, Åsa, 1962- (författare)
  • Food hypersensitivity among schoolchildren : prevalence, Health Related Quality of Life and experiences of double-blind placebo-controlled food challenges
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The prevalence of reported food hypersensitivity among children has increased in Western countries. However, the prevalence varies largely due to differences in methods used in different studies. Double-blind placebo-controlled food challenge (DBPCFC) is the most reliable method to verify or exclude food hypersensitivity. The use of double-blind food challenges is increasing in clinical praxis, but since the method is time- and resource consuming it is rarely used in population-based cohort studies. There is a lack of knowledge on how adolescents and mothers experience participation in double-blind placebocontrolled food challenges and to what extent the food is reintroduced after a negative challenge. While several studies have described the impact of IgEmediated food allergy on Health-Related Quality of Life (HRQL), few studies have described HRQL among children with other food hypersensitivity phenotypes.Aim: The aim of this thesis was to estimate the prevalence of reported food hypersensitivity, associated risk factors, and symptom expressions among schoolchildren. We also examined HRQL among children with total elimination of cow's milk, hen’s egg, fish or wheat due to food hypersensitivity as a group compared with children with unrestricted diet, and after we categorised the children with eliminated foods into different phenotypes of FHS. Finally, adolescents' and mothers' experience of DBPCFC was examined as well if the food had been reintroduced.Methods: Three studies were based on the Obstructive Lung Disease in Northern Sweden (OLIN) paediatric cohort II. The cohort was recruited in 2006 when all children in first and second grade (7-8 years) in three municipalities in Norrbotten were invited to a parental questionnaire study and 2,585 (96% of invited) participated. The questionnaire included questions about food hypersensitivity, asthma, rhinitis, eczema and possible risk factors. The children in two municipalities were also invited to skin prick testing with 10 airborne allergens, and 1,700 (90%) participated. Paper I is based on this initial survey of the cohort. Four years later, at age 11-12 years, the cohort was followed up using the same methods and with the same high participation rate. At the follow-up, 125 children (5% of the cohort) reported total elimination of cow's milk, hen's egg, fish or wheat due to food hypersensitivity. These children were invited to a clinical examination and to complete a generic (KIDSCREEN-52) and a diseasespecific HRQL questionnaire (FAQLQ-TF) (n=75). Based on the clinical examination the children were categorised into different phenotypes of food hypersensitivity: current food allergy, outgrown food allergy and lactose intolerance. In addition, a random sample of children with unrestricted diet from the same cohort, answered the generic questionnaire (n=209). Paper II is based on this HRQL study. Children categorised as having current food allergy were invited to a further evaluation including DBPCFC. Eighteen months after the challenges, these children were interviewed about their experiences during and after the challenge (n=17). Paper III is based on these interviews. Paper IV was based on interviews with mothers to children referred to a paediatric allergy specialist for evaluation of food allergy using DBPCFC (n=8). In the two interview studies results were analysed using qualitative content analysis.Results: At age 7-8 years, the prevalence of reported food hypersensitivity was 21%. Food hypersensitivity to milk, egg, fish, wheat or soy was reported by 10.9% and hypersensitivity to fruits or nuts by 14.6%. The most common essential food to trigger symptoms was milk, reported by 9%. The most frequently reported food induced symptoms, were oral symptoms mainly caused by fruits, followed by gastrointestinal symptoms mainly caused by milk. The risk factor pattern was different for food hypersensitivity to milk compared to hypersensitivity to other foods. No significant difference in distribution in generic or disease-specific HRQL was found among children with reported total elimination of milk, egg, fish and/or wheat due to FHS compared to children with unrestricted diet. However, a trend indicated that the disease-specific HRQL was most impaired among children with current food allergy compared to children with outgrown food allergy and lactose intolerance. The proportion of poor HRQL defined as ≥75 percentile was significantly higher among children with current food allergy than the other phenotypes. A DBPCFC was an opportunity for the adolescents and the mothers to overcome the fear of reactions to food that had been eliminated for a long time. After the challenge, when the food was partially or fully reintroduced, socializing became easier and both adolescents and mothers experienced more freedom regarding food intake. A negative challenge was not consistently associated with reintroduction of the food. Reasons for reintroduction failure were fear of allergic reactions, that the adolescent did not like the taste of the food, or that living with an elimination diet was considered as normal. Conclusion In this population-based study, one in five of children at age 7-8 years reported food hypersensitivity to any food. The generic HRQL was similar among children with and without food hypersensitivity. However, poor disease-specific HRQL was more common among children with current food allergy compared to children with other FHS phenotypes. If the tested food was reintroduced after a DBPCFC, both adolescents and mothers described a changed life with less fear, and that life had become easier regarding meal preparations and social events. As reintroduction failure was present despite a negative food challenge, follow-ups and evaluations of food reintroduction should be performed independent of the outcome of a food challenge.
  •  
50.
  • Strinnholm, Åsa, et al. (författare)
  • Food hypersensitivity is common in Swedish schoolchildren, especially oral reactions to fruit and gastrointestinal reactions to milk
  • 2014
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:12, s. 1290-1296
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: This study examined the prevalence, symptom expression and risk factors for food hypersensitivity among Swedish schoolchildren.METHODS: Parents of 2585 (96% of invited) children aged 7-8 years completed a questionnaire regarding food hypersensitivity and allergic diseases. A random sample of 1700 children (90% of invited) also participated in skin prick testing with ten airborne allergens.RESULTS: The overall prevalence of reported food hypersensitivity to milk, egg, fish, wheat, soya, fruits and, or, nuts was 21%, with symptoms caused by milk (9%) being the most common. The most frequently reported symptoms were oral symptoms (47.4%), mainly caused by fruit, and gastrointestinal symptoms (45.7%), mainly caused by milk. Factors associated with any food hypersensitivity were female sex, allergic heredity and a positive skin prick test. Eczema was consistently associated with symptoms caused by milk, egg, fish, wheat, soya, fruits and nuts. Rhinitis was associated to the same foods, except milk.CONCLUSION: Reported food hypersensitivity was common among Swedish schoolchildren. The most frequent symptom expressions were oral symptoms triggered by fruits and gastrointestinal symptoms triggered by milk. The high prevalence of reported symptoms should be validated by clinical examinations to provide a diagnosis.
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