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| 2. |
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| 3. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 4. |
- Svenugnsson, Elisabet, et al.
(författare)
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Decreased levels of autoantibodies against apolipoprotein B-100 antigens are associated with cardiovascular disease in systemic lupus erythematosus.
- 2015
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 181:3, s. 417-426
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Tidskriftsartikel (refereegranskat)abstract
- Increased production of autoantibodies is a characteristic feature of systemic lupus erythematosus (SLE) and there is evidence that several of these autoantibodies may contribute to the increased cardiovascular disease (CVD) in SLE. Autoantibodies against the apolipoprotein (apo) B-100 peptides p45 and p210 have been associated with a lower CVD risk in non-SLE cohorts. The aim of the present study was to investigate how SLE affects the occurrence of these potentially protective autoantibodies. The study cohort consisted of 434 SLE patients and 322 age and sex-matched population controls. Antibodies against native and malondialdehyde (MDA)-modified p45 and p210 were measured by ELISA. SLE patients had significantly lower levels of p210 IgG and p45 IgM (both the native and MDA-modified forms). SLE patients with manifest CVD (myocardial infarction, ischemic cerebrovascular disease or peripheral vascular disease) had lower levels p210 IgG and p45 IgM than SLE patients without CVD. Decreased levels of these autoantibodies were also observed in SLE patients with permanent organ damage as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI). The present findings show that patients with SLE, a condition generally characterized by abundance of autoantibodies of multiple specificities, have reduced levels of antibodies against the apo B-100 antigens p45 and p210 and that the levels of these antibodies are further reduced in SLE patients with CVD. These observations suggest the possibility that an impaired antibody-mediated removal of damaged LDL particles may contribute to the development of vascular complications and organ damage in SLE. This article is protected by copyright. All rights reserved.
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| 5. |
- Wigren, Maria, et al.
(författare)
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Cardiovascular disease in systemic lupus erythematosus is associated with increased levels of biomarkers reflecting receptor-activated apoptosis
- 2018
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 270, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: There is convincing evidence that adaptive immune responses affect the development of atherosclerosis and thrombosis and several autoimmune diseases are associated with increased cardiovascular risk. However, our understanding of the underlying mechanisms remains limited. We investigated how biomarkers reflecting four aspects of autoimmunity: apoptosis, inflammation, tissue degradation and repair, associate with cardiovascular disease (CVD) in subjects with systemic lupus erythematosus (SLE). Methods: We investigated 484 well-characterized SLE patients, 69 of whom had CVD (coronary artery disease, cerebrovascular disease or peripheral artery disease), and 253 controls. Occurrence of carotid plaques was investigated with ultrasound. Plasma levels of biomarkers reflecting apoptosis (Fas, TNF receptor 1, TRAIL receptor 2), inflammation (IL-6, IL-8, monocyte chemotactic protein-1), tissue degradation (matrix metalloproteinase (MMP)-1, MMP-3, MMP-7), and tissue repair (platelet-derived growth factor, epidermal growth factor and stem cell factor) were analyzed by Proximity Extension Assay. Results: Subjects with SLE had markedly elevated plasma levels of biomarkers reflecting apoptosis, inflammation and tissue degradation as compared to controls. SLE patients with CVD had higher levels of Fas, TNF receptor 1, TRAIL receptor 2, MMP-1 and -7 than those without CVD. The same associations were found for the presence of a carotid plaque. When controlling for the factors included in the Framingham risk score, all biomarkers except MMP-1 remained associated with the presence of a carotid plaque, while only TRAIL receptor 2 levels remained significantly associated with CVD. Conclusions: Our findings argue that the cardiovascular risk in SLE is associated with increased cell death by apoptosis and tissue degradation.
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| 6. |
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| 7. |
- Berglund, Ulla, et al.
(författare)
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Barnkartor blir planeringskartor
- 2010
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Ingår i: Den lärande staden. - 9789189140653 ; , s. 187-203
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Berglund, Ulla, et al.
(författare)
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Guide till barnkartor i GIS : ett verktyg för barns inflytande i stads- och trafikplanering
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det är väl känt att barn och unga vill vara med och på- verka sin närmiljö, och enligt FN:s barnkonvention har de rätt till det. Men barn kan inte delta i samhället på samma villkor som vuxna. Planering och förvaltning måste därför anpassa sina metoder till deras förutsättningar. Barnkartor i GIS är ett verktyg för att få med barns perspektiv i planering och förvaltning av vår gemensamma utomhusmiljö inklusive trafikmiljön. Vi har utvecklat en metod som ska vara snabb och lätt att använda och samtidigt ger trovärdiga och meningsfulla resultat för dem som ska ta emot och omsätta informationen. Planeraren ska själv, utan experthjälp, kunna använda metoden när hon/han vill få med barns och ungas perspektiv i sin verksamhet. Resultat ska vara enkla att få fram och gå smidigt att jämföra med andra data. Därför ska de lagras digitalt i planeringens vanliga geografiska informationssystem. (GIS = geografiskt informationssystem.) Det är, som vi förstått det, ett villkor för att barnens kunskap ska nå ända in i planeringen och inte ”hamna på hyllan”. Vårt motto för Barnkartor i GIS är att det ska vara en barnvänlig, skolvänlig och planeringsvänlig metod. Enkelhet och relevans i alla led är viktiga mål. Tillgänglighet via Internet och automatisk produktion av standardiserade temakartor innebär minskade krav på användarna och ger möjlighet för t.ex. en skola att själv ta initiativ till och genomföra ett projekt. Syftet kan då vara pedagogiskt men också ett led i att i att påverka i praktiken. Metoden ska underlätta för barns inflytande i planering av utemiljöns struktur och innehåll och dessutom ge underlag för prioriteringar inom förvaltning. Vi har anpassat den för den fördjupade översiktsplaneringen av stadsdelar eller mindre orter och för den planering av trafikmiljöer och förvaltning av utemiljö som görs på motsvarande nivå, t.ex. i förstudier till större projekt. Många resultat kan också användas på mer detaljerad nivå. Barnkartor i GIS är anpassad för barn från ca 10 år och för användning i skolor.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Brattsand, Göran, et al.
(författare)
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Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar -Något också för Norden?
- 2012
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Ingår i: Klinisk Biokemi i Norden. - 1101-2013. ; 24:4, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- Equalis och Svensk Förening för Klinisk Kemi (SFKK) rekommenderar att de kliniska laboratorierna i Sverige använder enhetliga måttenheter vid hormonbestämningar för ökad jämförbarhet och patientsäkerhet. Vid analys i serum eller plasma med nuvarande metoder rekommenderas följande enheter:• Adrenokortikotropt hormon (ACTH): pmol/L• Insulin: mIE/L• Parathormon (PTH): pmol/L• Prolaktin: mIE/L• Tillväxthormon (GH): μg/L• Östradiol: pmol/L• Aldosteron: pmol/L• Reninkoncentration: mIE/L
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| 13. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 14. |
- Eriksson, Daniel, et al.
(författare)
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Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison’s disease in Sweden
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.
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| 15. |
- Erlandsson, Kerstin, et al.
(författare)
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Experiences of gay women during their partner's pregnancy and childbirth
- 2010
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Ingår i: British journal of midwifery. - : MA Healthcare Ltd. - 0969-4900 .- 2052-4307. ; 18:2, s. 99-103
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Tidskriftsartikel (refereegranskat)abstract
- Growing numbers of openly gay women choose to have children, but there have been few studies on the topic. The aim of this study was to describe the co-mother's experiences of care provided during their partner's pregnancy, childbirth and the postnatal period. Six co-mothers were interviewed between six weeks and three years after the birth of their child. The open interviews were analysed using content analysis. The overall theme of the findings was 'like everyone else, but not quite'. The following main categories were identified: need for acknowledgement, need for care designed to suit same-sex couples, and in the hands of nursing staff. Co-mothers felt themselves to be 'like everyone else but not quite'. In order to support the relationship of same-sex parents in parenthood it is important for midwifery staff to recognize co-mothers as an equal parent of the child
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| 16. |
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| 17. |
- Erlandsson, Kerstin, et al.
(författare)
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Qualitative interviews with adolescents about "Friends-with-Benefits" relationships
- 2013
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Ingår i: Public Health Nursing. - : Wiley-Blackwell. - 0737-1209 .- 1525-1446. ; 30:1, s. 47-57
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the thoughts, reflections, and experiences of friends-with-benefits relationships among a group of Swedish adolescents. Design and Sample: A qualitative study with an explorative and descriptive design. Eight adolescents, aged 16-18, were interviewed. Measures: Individual in-depth interviews were undertaken. Data were analyzed using latent content analysis. Results: The informants involved themselves in Friends-with-benefits (FWB) relationships to find physical and psychological intimacy without any expectations or demands. FWB relationships were perceived to have more advantages when the partner was a close friend with whom an informant felt comfortable. There was ambivalence about the legitimacy of romantic feelings in an FWB relationship, although it was quite common. Sexual concurrency was common and often accepted. Sexual risk-taking behavior involving the use of alcohol and a lack of contraception was considered common in FWB relationships. Informants requested more education and support as regards their sexual behavior. Conclusions: FWB relationships were often initiated to find physical and psychological intimacy with no expectations or demands. Advantages such as sexual concurrency and no demands were central. A deeper understanding of how adolescents think and reason about sexuality and relationships can make a difference when working to improve young people's sexual and reproductive health.
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| 18. |
- Henriksson, Eva, et al.
(författare)
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Salt stress signalling and the role of calcium in the regulation of the Arabidopsis ATHB7 gene
- 2005
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Ingår i: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 28:2, s. 202-210
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Tidskriftsartikel (refereegranskat)abstract
- In plants changes in cytosolic calcium ion concentrations ([Ca2+]cyt) have been detected after various stress treatments, including salt treatment. The involvement of a Ca2+ signal as an essential component of signalling pathways leading to downstream responses, such as gene expression, is supported only by a few studies. In this study the possible involvement of the salt stress-induced increase in [Ca2+]cyt in the signalling pathway leading to the induction of ATHB7, a homeobox gene encoding a homeodomain leucine zipper (HDZip) transcription factor was analysed. The salt-induced expression of ATHB7 was found to be independent of the Ca2+ signal evoked by salt. Instead, it was found that ATHB7 expression in shoots was not dependent on a direct contact with salt or osmoticum, whereas in roots, ATHB7 seemed to be induced by the direct contact, indicating that signals from roots cause systemic induction of ATHB7. Abscisic acid (ABA) or ABA-dependent components were found to, at least partly, to function as the systemic signal.
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| 19. |
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| 20. |
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| 21. |
- Mathioudaki, Argyri, Ph.D student, 1986-, et al.
(författare)
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Allele frequency spectrum of known ankylosing spondylitis associated variants in a Swedish population
- 2022
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 51:1, s. 21-24
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The genetic predisposition to ankylosing spondylitis (AS) has been most widely studied in cohorts with European ancestry. However, within Europe, disease prevalence is higher in Sweden. Given this, we aimed to characterize known AS susceptibility variants in a homogeneous Swedish data set, assessing reproducibility and direction of effect. Method: The power to detect association within an existing Swedish targeted sequencing study (381 controls; 310 AS cases) was examined, and a set of published associations (n = 151) was intersected with available genotypes. Association to disease was calculated using logistic regression accounting for population structure, and HLA-B27 status was determined with direct polymerase chain reaction genotyping. Results: The cases were found to be 92.3% HLA-B27 positive, with the data set showing >= 80% predictive power to replicate associations, with odds ratios >= 1.6 over a range of allele frequencies (0.1-0.7). Thirty-four markers, representing 23 gene loci, were available for investigation. The replicated variants tagged MICA and IL23R loci (p < 1.47 x 10(-3)), with variable direction of effect noted for gene loci IL1R1 and MST1. Conclusion: The Swedish data set successfully replicated both major histocompatibility complex (MHC) and non-MHC loci, and revealed a different replication pattern compared to discovery data sets. This was possibly due to population demographics, including HLA-B27 frequency and measured comorbidities.
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| 22. |
- Mathioudaki, Argyri, Ph.D student, 1986-, et al.
(författare)
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Replication and fine mapping of ankylosing spondylitis replicated loci in the Swedish population reveal different CCHCR1 protective haplotypes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The genetics of ankylosing spondylitis (AS) derives mainly from studies performed in large cohorts of British origin. However, within Europe, disease prevalence is higher in Sweden, and so we investigated the reproducibility of known AS susceptibility patterns in a homogeneous Swedish cohort.Methods: The replication power of the Swedish cohort was examined and a set of published SNP associations intersected with genotypes from an existing targeted sequencing study using these individuals (381 controls; 310 AS cases). To elucidate whether replication patterns derived from population subsampling or genetic similarity, allele frequency data from additional British and Swedish control populations were examined for genetic differentiation (FST). Replicated loci were fine mapped to investigate associations in more detail, and signals were dissected with haplotype analysis and functional annotation.Results: The study had 80% power to find variants of strong effect (Odds ratio, OR>2) given a wide range of risk allele frequencies (0.2-3), tagging HLA-B,CCHCR1and IL23R. The replication pattern was not due to European population genetic distance and fine mapping revealed genome-wide repositioned associations in HLA-Band CCHCR1, independent from the published associations (p-value < 2 x10-8, r2 < 0.3). The CCHCR1 locus showed two protective haplotype blocks (B1-1 and B2-1), independent from HLA-B signals (B1-1: r2 = 0.39, B2-2:r2=0.07), where 74% of controls were carrying 2 copies of the protective haplotypes (B1-1 and B2-1: OR=0.3, p-value = 1.2 x 10-45). Interestingly, while both haplotypes span CCHCR1, the effect of each haplotype is likely in cis, with eQTL evidence pointing to the regulation of TCF19(B1-1) and POU5F1(B1-2).Conclusions: Both European populations share key disease loci, but the Swedish cohort revealed fine-scale genetic differences, that may point to gene regulation. This study utilized a different variant resolution, and by doing so demonstrated that smaller populations have the potential to reveal new AS pathogenesis mechanisms and that further study of the Swedish population is warranted.
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| 23. |
- Mathioudaki, Argyri, Ph.D student, 1986-, et al.
(författare)
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Targeted sequencing reveals the somatic mutation landscape in a Swedish breast cancer cohort
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) is a genetically heterogeneous disease with high prevalence in Northern Europe. However, there has been no detailed investigation into the Scandinavian somatic landscape. Here, in a homogeneous Swedish cohort, we describe the somatic events underlying BC, leveraging a targeted next-generation sequencing approach. We designed a 20.5 Mb array targeting coding and regulatory regions of genes with a known role in BC (n = 765). The selected genes were either from human BC studies (n = 294) or from within canine mammary tumor associated regions (n = 471). A set of predominantly estrogen receptor positive tumors (ER + 85%) and their normal tissue counterparts (n = 61) were sequenced to ~ 140 × and 85 × mean target coverage, respectively. MuTect2 and VarScan2 were employed to detect single nucleotide variants (SNVs) and copy number aberrations (CNAs), while MutSigCV (SNVs) and GISTIC (CNAs) algorithms estimated the significance of recurrent somatic events. The significantly mutated genes (q ≤ 0.01) were PIK3CA (28% of patients), TP53 (21%) and CDH1 (11%). However, histone modifying genes contained the largest number of variants (KMT2C and ARID1A, together 28%). Mutations in KMT2C were mutually exclusive with PI3KCA mutations (p ≤ 0. 001) and half of these affect the formation of a functional PHD domain. The tumor suppressor CDK10 was deleted in 80% of the cohort while the oncogene MDM4 was amplified. Mutational signature analyses pointed towards APOBEC deaminase activity (COSMIC signature 2) and DNA mismatch repair (COSMIC signature 6). We noticed two significantly distinct patterns related to patient age; TP53 being more mutated in the younger group (29% vs 9% of patients) and CDH23 mutations were absent from the older group. The increased somatic mutation prevalence in the histone modifying genes KMT2C and ARID1A distinguishes the Swedish cohort from previous studies. KMT2C regulates enhancer activation and assists tumor proliferation in a hormone-rich environment, possibly pointing to a role in ER + BC, especially in older cases. Finally, age of onset appears to affect the mutational landscape suggesting that a larger age-diverse population incorporating more molecular subtypes should be studied to elucidate the underlying mechanisms.
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| 24. |
- Mathioudaki, Argyri, Ph.D student, 1986-, et al.
(författare)
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The sex-stratified genetic architecture of ankylosing spondylitis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Sexual dimorphism is an emerging feature of ankylosing spondylitis (AS), a chronic rheumatic condition affecting upto three times more men than women. Using 691 individuals from a Swedish case-control cohort, we revealed thatsex biases are also a hallmark of AS genetic predisposition, and that this multifactorial disease is in part driven byboth rare and common variants. We identified SNPs via the targeted re-sequencing of 7 270 coding and non-codingloci, and assessed novel patterns of association with both single marker and aggregate loci SKAT tests. The malespecific RUNX3 locus (including rs7414934, OR=2.58, p=1.7x10-5) and female specific MICB SKAT locus (27variants, p=1.2x10-6; rs3828903, OR=4.62, p=6.2x10-13) exceeded discovery thresholds. Multiple risk variants fromeach locus were shown to be functionally active in immune (Jurkat), skin (HaCat) and bone (SaOS-2) cell lines.Differential patterns of genetic predisposition may point to alternative disease mechanisms in male and femalepatients. Genetic and functional analyses demonstrated that risk alleles should not be considered in isolation and thatassociated variants would likely affect gene regulation across multiple tissues. This work illustrates the need toconsider the contribution of sex to the genetics of AS and the duality that individual loci may play in the key clinical outcomes of disease.
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| 25. |
- Nordin, Annica, et al.
(författare)
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Ischemic arterial events and atherosclerosis in patients with systemic sclerosis : a population based case-control study
- 2013
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 15, s. R87-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: While microvascular disease is well described in systemic sclerosis (SSc), it is still unclear whether the occurrence of ischemic macrovascular events and atherosclerosis is enhanced among patients with SSc.METHODS: In this study, 111 SSc patients (74 % of prevalent cases in Stockholm County) and 105 age and sex comparable population controls were investigated. Previous ischemic arterial events were tabulated. As surrogate measures of atherosclerosis, plaque occurrence and intima media thickness (IMT) were determined with carotid ultrasound and the ankle brachial index (ABI) was calculated. Traditional cardiovascular risk factors were recorded and we also measured biomarkers indicating systemic inflammation and endothelial activation/dysfunction.RESULTS: Mean age was 62 +/- 12 years for patients and controls. Ischemic arterial events were more common, due to increased occurrence of ischemic heart disease (IHD) and ischemic peripheral vascular disease (IPVD), in the patient group (12% vs. 4% p=0.03 and 9% vs. 0%, P=0.003 respectively). On a group level there was no difference regarding the occurrence of ischemic cerebrovascular disease, the frequency of plaques, IMT or ABI between SSc patients and controls. Subgroup analyses revealed that patients with anti-centromere antibodies (ACA+) had more plaques and more ischemic arterial events compared to other SSc patients (67% vs. 39% and 32% vs. 11%; P=0.006 and P=0.01, respectively) and compared to controls (67% vs. 41% and 32% vs. 7%, P=0.02 and P=0.0003, respectively). Biomarkers of inflammation/endothelial activation were generally increased among SSc patients.CONCLUSIONS: Patients with SSc are at enhanced risk for IHD and IPVD. The ACA+ SSc subgroup was particularly affected with both ischemic arterial events and premature atherosclerosis. The microvascular vulnerability of ACA+ patients is previously well documented. We demonstrate that ACA+ SSc patients have an enhanced risk of macrovascular injury as well. This group should be followed closely and modifiable cardiovascular risk factors should be treated at an early stage.
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| 26. |
- Nordin, Jessika, et al.
(författare)
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Association of Protective HLA-A With HLA-B∗27 Positive Ankylosing Spondylitis
- 2021
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Ingår i: Frontiers in Genetics. - Lausanne, Switzerland : Frontiers Media S.A.. - 1664-8021. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To further elucidate the role of the MHC in ankylosing spondylitis by typing 17 genes, searching for HLA-B∗27 independent associations and assessing the impact of sex on this male biased disease.Methods: High-confidence two-field resolution genotyping was performed on 310 cases and 2196 controls using an n-1 concordance method. Protein-coding variants were called from next-generation sequencing reads using up to four software programs and the consensus result recorded. Logistic regression tests were applied to the dataset as a whole, and also in stratified sets based on sex or HLA-B∗27 status. The amino acids driving association were also examined.Results: Twenty-five HLA protein-coding variants were significantly associated to disease in the population. Three novel protective associations were found in a HLA-B∗27 positive population, HLA-A∗24:02 (OR = 0.4, CI = 0.2–0.7), and HLA-A amino acids Leu95 and Gln156. We identified a key set of seven loci that were common to both sexes, and robust to change in sample size. Stratifying by sex uncovered three novel risk variants restricted to the female population (HLA-DQA1∗04.01, -DQB1∗04:02, -DRB1∗08:01; OR = 2.4–3.1). We also uncovered a set of neutral variants in the female population, which in turn conferred strong effects in the male set, highlighting how population composition can lead to the masking of true associations.Conclusion: Population stratification allowed for a nuanced investigation into the tightly linked MHC region, revealing novel HLA-B∗27 signals as well as replicating previous HLA-B∗27 dependent results. This dissection of signals may help to elucidate sex biased disease predisposition and clinical progression.
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| 27. |
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| 28. |
- Nordin, Jessika
(författare)
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Human leukocyte antigen in sickness and in health : Ankylosing spondylitis and HLA in Sweden
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human leukocyte antigen (HLA) plays a major role in keeping us healthy, but some of the HLA alleles can contribute to disease susceptibility. One example is HLA-B*27, which confers increased susceptibility of ankylosing spondylitis and represents one of the strongest genetic associations found in any common human disease. Ankylosing spondylitis shows a strong sex ratio skew (2-3:1 male to female) and studies confirm the existence of sexual-dimorphism in the presentation of this disease. The genetic predisposition for this, however, has not previously been studied. A Swedish ankylosing spondylitis population was sequenced with a targeted array to investigate the existence of sex-specific associations. RUNX3 was revealed to be associated in males by a univariate test, while aggregate tests revealed the HLA gene MICB to be associated in females. Functional validation demonstrated that the risk variants in RUNX3 increase expression, and MICB changed the transcription factor binding sites. Interestingly, since the disease involves bone changes, both RUNX3 and one of the MICB variants had effect in the bone cell line, SaOS-2.In order to help researchers obtain more controls for HLA analysis, an HLA allele bioresource (SweHLA) was generated from 1,000 Swedish genomes. The alleles were typed with three to four HLA typing software programs and results were combined by an n-1methodology. This produced high quality alleles where the bias from each software program was diminished.The methodology from SweHLA was utilised to study HLA in ankylosing spondylitis. To investigate both sex-specific predisposition and HLA-B*27 independence, samples were subdivided into two populations (one population with mixed HLA-B*27 positive and negative samples and one with only HLA-B*27 positive samples) that in turn were grouped by sex. In the mixed population, several alleles were replicated from previous studies. This study also revealed three female-specific alleles, two of which were new and one that had previously been associated to the severity of radiological changes. The HLA-B*27 population revealed a previously unknown protective allele, HLA-A*24:02. Through deeper examination of the HLA-B*27 population, two amino acids in HLA-A, position 119 in the whole set and position 180 in the male set, were revealed to be protective.This thesis brings new insight into the genetic predisposition for a sex-skewed disease, demonstrating how sexual-dimorphism can be reflected in the genetic predisposition, hopefully leading to more similar studies. It also highlights the importance of methodology and demonstrate the drastic biases that can be imparted by software programs.
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| 29. |
- Nordin, Jessika, et al.
(författare)
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SweHLA : the high confidence HLA typing bio-resource drawn from 1000 Swedish genomes
- 2020
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 28:5, s. 627-635
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Tidskriftsartikel (refereegranskat)abstract
- There is a need to accurately call human leukocyte antigen (HLA) genes from existing short-read sequencing data, however there is no single solution that matches the gold standard of Sanger sequenced lab typing. Here we aimed to combine results from available software programs, minimizing the biases of applied algorithm and HLA reference. The result is a robust HLA population resource for the published 1000 Swedish genomes, and a framework for future HLA interrogation. HLA 2nd-field alleles were called using four imputation and inference methods for the classical eight genes (class I: HLA-A, HLA-B, HLA-C; class II: HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1). A high confidence population set (SweHLA) was determined using an n−1 concordance rule for class I (four software) and class II (three software) alleles. Results were compared across populations and individual programs benchmarked to SweHLA. Per gene, 875 to 988 of the 1000 samples were genotyped in SweHLA; 920 samples had at least seven loci called. While a small fraction of reference alleles were common to all software (class I = 1.9% and class II = 4.1%), this did not affect the overall call rate. Gene-level concordance was high compared to European populations (>0.83%), with COX and PGF the dominant SweHLA haplotypes. We noted that 15/18 discordant alleles (delta allele frequency >2) were previously reported as disease-associated. These differences could in part explain across-study genetic replication failures, reinforcing the need to use multiple software solutions. SweHLA demonstrates a way to use existing NGS data to generate a population resource agnostic to individual HLA software biases.
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| 30. |
- Nordin, Karin, et al.
(författare)
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Adolescents’ experiences of obesity surgery : a qualitative study
- 2018
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289 .- 1878-7533. ; 14:8, s. 1157-1162
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The positive effects of behavioural treatment and weight management in adolescents with severe obesity are modest. Obesity surgery can be an option for adolescents, but is not the first-hand choice of treatment. The knowledge about adolescents' own experiences of having undergone surgery and their thoughts and feelings of the follow-up period are limited.OBJECTIVES:To describe adolescents' decision to go through obesity surgery as teenager and their experiences of the follow-up period.SETTING:National Childhood Obesity Centre at Karolinska University Hospital in Stockholm, Sweden.METHODS:Phone interviews with 20 young adults that went through obesity surgery as teenagers. Interviews were analysed with qualitative systematic text condensation.RESULTS:"Lost in the healthcare system" and "A rough but well worth journey to a healthier life" were the categories that appeared in our analysis. The participant had a feeling of uncertainty about contacts with the healthcare system and the transition to primary care was confusing. Most of the participants were happy with the decision to go through obesity surgery as teenager, despite it had been a difficult time.CONCLUSIONS:Our results show implications for improving the clinical care of adolescents undergoing obesity surgery, which should be offered as a last choice. Information and individualized supports should be offered more often during first year postsurgery and should be given by a multidisciplinary team. This multifaceted population should be given priority for a successful transition.
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| 31. |
- Nordin, Kerstin
(författare)
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Att sätta barn på kartan : barnkartor i GIS – för information om barns utemiljö
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Utemiljön utgör en viktig del i många barns liv och FN:s konvention om barnets rättigheter ger barn rätt att höras i frågor som rör dem. Men ett flertal studier visar att det trots ett uttalat intresse hos många politiker och planerare är svårt att få frågor som berör barns utemiljö beaktade i kommunal, fysisk planering. I avhandlingen undersöks vilka hinder och möjligheter som kan finnas för att information om barns utemiljö ska bli mer använd i det sammanhanget. Geografiska informationssystem (GIS) och kartor spelar en viktig roll i fysisk planering, vilket har tagits som utgångspunkt för att utforma en metod som kan fungera i kommunal planering och ge relevant information om barns utemiljö på ett sätt som tar tillvara barns kompetens och respekterar deras rättigheter. Det forskningsprojekt som avhandlingen bygger på är ett exempel på design som forskningsstrategi. Forskning genom design innebär, i det här fallet, att i en iterativ, reflekterande process utveckla såväl en metod, som de konceptuella föreställningar som forskningsprojektet bygger på. Metoden Barnkartor i GIS är ett resultat av forskningsprojektet. Metoden består av en digital kartenkät med frågor till barn från 10 års ålder om hur utemiljön används, upplevs och kan förbättras. En variant av enkäten ställer frågor till lärare om hur skolans utemiljö används i undervisningen. Enkäten besvaras i skolan och med en handledare närvarande. Dessutom består metoden av en speciellt utformad GIS-applikation samt en procedur för en etisk och säker informationsprocess. I avhandlingen redovisas erfarenheter från de fem kommuner som använt metoden Barnkartor i GIS i konkreta planeringsprojekt. Det visade sig att information om barns utemiljö efterfrågades av planerare med sinsemellan olika perspektiv på planering, utemiljö och kartor, men även tillgång till GIS-teknik och GIS-kompetens varierade. En modell för att göra enkätsvaren tillgängliga för alla intresserade redovisas i avhandlingen. Studierna indikerar också att det finns såväl tekniska, administrativa och konceptuella begränsningar för att information om barns utemiljö ska kunna användas av intresserade planerare. I avhandlingen uppmärksammas betydelsen av de erfarenheter som användare av metoden får i mötet med barn och den kunskap som barnen delar med sig av. Det ses som en strategisk tillgång för att utveckla ett barnperspektiv i kommunal, fysisk planering och andra verksamheter som påverkar barns utemiljö.
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| 32. |
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| 33. |
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| 34. |
- Nordin, Kerstin
(författare)
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Barnkartor i GIS
- 2019
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Ingår i: Movium Fakta. - 2001-2357.
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Annan publikation (populärvet., debatt m.m.)
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| 35. |
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| 36. |
- Nordin, Kerstin, et al.
(författare)
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Children's Maps in GIS: A Tool for Communicating Outdoor Experiences in Urban Planning
- 2013
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Ingår i: Digital literacy: concepts, methodologies, tools, and applications. - : IGI Global. - 9781466620384 ; , s. 799-814
-
Bokkapitel (refereegranskat)abstract
- Since 2002 the authors have successively developed "Children's Maps in GIS", a method for children's participation in spatial planning. Their studies show that 10-15 year-olds are capable of reading maps and using a GIS-application for communicating their interests in a stable and useful manner. The purpose of this article is to discuss the first stages of implementation in a real world project, in relation to ICT. The authors report experiences from a Swedish municipality using Children's Maps in GIS in a survey with over 600 children as part of a comprehensive planning process and give examples of how data can be visualized. A significant digital divide between different parts of the administration is noted. In the ongoing development into an Internet version of the method the authors aim to increase the access to the GIS-application and develop standard procedures for categorizing and analyzing data.
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| 37. |
- Nordin, Kerstin, et al.
(författare)
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Children’s Maps in GIS - a tool for communication outdoor experiences in urban planning
- 2010
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Ingår i: International Journal of Information Communication Technologies and Human Development. - 1935-5661. ; 2, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Since 2002 the authors have successively developed “Children’s Maps in GIS”, a method for children’s participation in spatial planning. Their studies show that 10-15 year-olds are capable of reading maps and using a GIS-application for communicating their interests in a stable and useful manner. The purpose of this article is to discuss the first stages of implementation in a real world project, in relation to ICT. The authors report experiences from a Swedish municipality using Children’s Maps in GIS in a survey with over 600 children as part of a comprehensive planning process and give examples of how data can be visualized. A significant digital divide between different parts of the administration is noted. In the ongoing development into an Internet version of the method the authors aim to increase the access to the GIS-application and develop standard procedures for categorizing and analyzing data
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| 38. |
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| 39. |
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| 40. |
- Nordin, Kerstin
(författare)
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Visualising Outdoor Environment from the Perspectives of Children and Teachers
- 2017
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Ingår i: The Nordic Journal of Architectural Research. - 1893-5281. ; , s. 169 - 196
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Tidskriftsartikel (refereegranskat)abstract
- This study forms part of a Swedish research project aiming to design a method (“Children’s Maps in GIS”) for consulting children and teachers on children’s outdoor environment to inform actors in urban planning processes in a local authority. Following up on consultation projects at four local authorities in Sweden, users of the method identified problems with communicating the results to the heterogeneous group of actors in urban planning dealing with children’s outdoor environment. One constraint was lack of examples demonstrating how non-cartographic information in a database can be analysed and visualised.This study provides such an example based on information from the municipality of Västerås, Sweden, where 90 children aged 10–11 and six teachers were responding on a facilitated map questionnaire included in “Children’s Maps in GIS”. The results obtained were visualised and presented to and discussed with urban planners in Västerås.Drawing on results from the meeting with the planners, theories on how children communicate experiences of place and the role of information in communicative planning practices a conceptual visualisation model where developed. The study indicates that the challenge is what to include in the guidelines to take responsibility for the entire communication process.
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| 41. |
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| 42. |
- Roy, Ananya, et al.
(författare)
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Using evolutionary constraint to define novel candidate driver genes in medulloblastoma
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:33
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Tidskriftsartikel (refereegranskat)abstract
- Current knowledge of cancer genomics remains biased against noncoding mutations. To systematically search for regulatory noncoding mutations, we assessed mutations in conserved positions in the genome under the assumption that these are more likely to be functional than mutations in positions with low conservation. To this end, we use whole-genome sequencing data from the International Cancer Genome Consortium and combined it with evolutionary constraint inferred from 240 mammals, to identify genes enriched in noncoding constraint mutations (NCCMs), mutations likely to be regulatory in nature. We compare medulloblastoma (MB), which is malignant, to pilocytic astrocytoma (PA), a primarily benign tumor, and find highly different NCCM frequencies between the two, in agreement with the fact that malignant cancers tend to have more mutations. In PA, a high NCCM frequency only affects the BRAF locus, which is the most commonly mutated gene in PA. In contrast, in MB, >500 genes have high levels of NCCMs. Intriguingly, several loci with NCCMs in MB are associated with different ages of onset, such as the HOXB cluster in young MB patients. In adult patients, NCCMs occurred in, e.g., the WASF-2/ AHDC1/FGR locus. One of these NCCMs led to increased expression of the SRC kinase FGR and augmented responsiveness of MB cells to dasatinib, a SRC kinase inhibitor. Our analysis thus points to different molecular pathways in different patient groups. These newly identified putative candidate driver mutations may aid in patient stratification in MB and could be valuable for future selection of personalized treatment options.
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| 43. |
- Sullivan, Patrick F., et al.
(författare)
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Leveraging base-pair mammalian constraint to understand genetic variation and human disease
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643, s. 367-
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.
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| 44. |
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| 45. |
- Wang, Chao, et al.
(författare)
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A novel canine reference genome resolves genomic architecture and uncovers transcript complexity
- 2021
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- We present GSD_1.0, a high-quality domestic dog reference genome with chromosome length scaffolds and contiguity increased 55-fold over CanFam3.1. Annotation with generated and existing long and short read RNA-seq, miRNA-seq and ATAC-seq, revealed that 32.1% of lifted over CanFam3.1 gaps harboured previously hidden functional elements, including promoters, genes and miRNAs in GSD_1.0. A catalogue of canine "dark" regions was made to facilitate mapping rescue. Alignment in these regions is difficult, but we demonstrate that they harbour trait-associated variation. Key genomic regions were completed, including the Dog Leucocyte Antigen (DLA), T Cell Receptor (TCR) and 366 COSMIC cancer genes. 10x linked-read sequencing of 27 dogs (19 breeds) uncovered 22.1 million SNPs, indels and larger structural variants. Subsequent intersection with protein coding genes showed that 1.4% of these could directly influence gene products, and so provide a source of normal or aberrant phenotypic modifications. Here, the authors report an improved de novo reference genome for the domestic dog based on a female German Shepherd named Mischka. The new genome increases contiguity 55-fold over the previous dog assembly and uncovers functional elements that were not previously identifiable.
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| 46. |
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| 47. |
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