| 1. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 2. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 3. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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| 4. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 5. |
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| 6. |
- Crosby, Jacy, et al.
(författare)
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Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
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| 7. |
- Ekman, Sirkka-Liisa, et al.
(författare)
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Alzheimer
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Hamacher-Barth, Evelyne, et al.
(författare)
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A method for sizing submicrometer particles in air collected on Formvar films and imaged by scanning electron microscopy
- 2013
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 6:12, s. 3459-3475
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Tidskriftsartikel (refereegranskat)abstract
- A method was developed to systematically investigate individual aerosol particles collected onto a polyvinyl formal (Formvar)-coated copper grid with scanning electron microscopy. At very mild conditions with a low accelerating voltage of 2 kV and Gentle Beam mode aerosol particles down to 20 nm in diameter can be observed. Subsequent processing of the images with digital image analysis provides size resolved and morphological information (elongation, circularity) on the aerosol particle population. Polystyrene nanospheres in the expected size range of the ambient aerosol particles (20–900 nm in diameter) were used to confirm the accuracy of sizing and determination of morphological parameters. The relative standard deviation of the diameters of the spheres was better than ±10% for sizes larger than 40 nm and ±18% for 21 nm particles compared to the manufacturer's certificate. Atmospheric particles were collected during an icebreaker expedition to the high Arctic (north of 80°) in the summer of 2008. Two samples collected during two different meteorological regimes were analyzed. Their size distributions were compared with simultaneously collected size distributions from a Twin Differential Mobility Particle Sizer, which confirmed that a representative fraction of the aerosol particles was imaged under the electron microscope. The size distributions obtained by scanning electron microscopy showed good agreement with the Twin Differential Mobility Sizer in the Aitken mode, whereas in the accumulation mode the size determination was critically dependent on the contrast of the aerosol with the Formvar-coated copper grid. The morphological properties (elongation, circularity) changed with the number of days the air masses spent over the pack-ice area north of 80° before the aerosol particles were collected at the position of the icebreaker and are thus an appropriate measure to characterize transformation processes of ambient aerosol particles.
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| 9. |
- Haux, Caroline, 1960-
(författare)
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Framkallning : Skrift, konsumtion och sexualitet i Karin Boyes Astarte och Henry Parlands Sönder
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is a comparative study in two novels which both try to understand modern life. The novels were both written between 1929 and 1930 as entries for the same major Nordic novel contest – Astarte in Sweden by Karin Boye, Sönder [To Pieces ]in Finland by the Finno-swedish author Henry Parland.This analysis tries to determine what is at stake in these novels by, apart from investigating them as novels in their own right, examining the complex interaction between a specific moment in history and the representation of that moment as literary text. The novels are examined as events in a specific historical situation; that is, how they write what is contemporary into themselves, trough answering the question about the historical moment that they themselves formulate. Four issues are fundamental to the study: The function of consumption and the commodity form in the novels. The way in which these novels render sexuality and desire. How other media forms function as aesthetic technologies for the novels. Lastly, aesthetics, writing and allegory: how the novels reflect on the possibility of representing this societal moment in history.A focus in the analysis is how woman is called forth as golden statue and photography, how she by letting herself be consumed as sexual symbol elicits male speech – thereby also making the speaker into author, and man. The economic side to this is the way in which men and women take on the form of commodities amongst themselves. It is in this sexual economy that they become men and women. The transformation of the sexed object into the systematic status of a sign, signifying its value, implies the simultaneous transformation of human relations into consumer relations: You consume or get consumed.
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| 10. |
- Jansson, Caroline, et al.
(författare)
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A Swedish study of midwives' and nurses' experiences when women are diagnosed with a missed miscarriage during a routine ultrasound scan
- 2010
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Ingår i: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 1:2, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to describe midwives' and nurses' experiences when women are diagnosed with a missed miscarriage during a routine ultrasound scan in pregnancy weeks 18-20.STUDY DESIGNS: A qualitative content analysis with an inductive approach and 13 semi-structured interviews were used for data collection from these three domains: midwives at an ultrasound department, midwives at a maternity clinic and nurses at a gynecological ward. Content analysis resulted in six codes, four categories and one primary theme.MAIN OUTCOME MEASURES: The four categories identified were: the interviewees' experiences of women's reactions, support from the midwife and nurse, the interviewees' experiences of men's reactions and communication between care providers and women. The main theme focused on the interviewees' noting that women had a premonition that something was wrong with their pregnancy. This could for example have been in the form of minor bleeding or the fact that pregnancy symptoms had receded and there were no movements by the fetus. The midwives carried out a follow-up with assessment.CONCLUSIONS: Women need confirmation of their premonitions of a missed miscarriage so that a diagnosis can be made as early as possible in their pregnancy. Women and their partners who have suffered a missed miscarriage need extended support on an individual basis in addition to follow-up assistance as assessed by the midwives.
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| 11. |
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| 12. |
- Jansson, Caroline, et al.
(författare)
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Application of “Swanson’s middle range caring theory” in Sweden after miscarriage
- 2011
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Ingår i: International Journal of Clinical Medicine. - : Scientific Research Publishing. - 2158-284X .- 2158-2882. ; 2:2, s. 102-109
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to apply Swanson’s Middle Range Caring Theory to the follow-up visit with a midwife for Swedish women who have suffered early miscarriage or received care for late missed miscarriage in pregnancy week 18 - 20. Methods: Twenty-five tape recorded interviews with women four weeks after their early miscarriages and thirteen tape recorded semi-structured interviews with midwives and nurses who had the experience of caring for women who have been diagnosed with a missed miscarriage during a routine ultrasound scan. The interviews were transcribed verbatim and interpreted deductively from the text using the theory. Results : Each woman described her personal experience of miscarriage in the relative terms of a human experience. The midwives and nurses described their experiences with women who received care for missed miscarriage. The interviews included information about the treatment provided by the caregivers during the period afterward of the diagnosis. The caregiver attitude was formed from Swanson’s caring categories: “Maintaining belief”, “knowing”, “being with”, “doing for”, “enabling”. Conclusions: Swanson’s Middle Range Caring Theory as applied to the caregiver includes being emotionally present, giving support with respect for the woman’s dignity, being competent, meeting each woman’s own individual needs. Given the proper care after a miscarriage every woman has the power within herself to improve their wellbeing.
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| 13. |
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| 14. |
- Jansson, Leif, et al.
(författare)
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Functional stimulation of graft nerves has minor effects on insulin release from transplanted rat pancreatic islets
- 2013
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 118:4, s. 209-216
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Morphological evidence for reinnervation of pancreatic islet grafts is plentiful. However, to what extent intra-graft nerves influence the endocrine functions of the islet transplant is largely unknown. We therefore aimed to directly stimulate nerves leading to islet grafts with electrodes and measure insulin secretion in response to this.Methods. We implanted syngeneic islets under the renal capsule of rats, and examined them 1 or 7-9 months later. In anesthetized rats blood samples were collected from the renal vein and femoral artery, respectively, during electrode stimulation of the nerves leading to the islet grafts. Results. As expected, nerve stimulation decreased renal blood flow. However, serum insulin concentrations in samples derived from the renal vein or femoral artery changed in concert with one another, both during normoglycemia and acute hyperglycemia.Conclusion. Reinnervation which occurs after islet transplantation under the renal capsule has minor effects on graft endocrine function.
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| 15. |
- Jansson, Lasse, et al.
(författare)
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Traumatisering bland ungdomar med antisocial problematik : Resultat från en litteraturöversikt
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Att ha blivit traumatiserad betyder att skrämmande upplevelser av till exempel våld har lett till allvarlig psykisk ohälsa hos en individ. Denna rapport är en systematisk kunskapsöversikt över traumatisering bland institutionsvårdade ungdomar. Internationella vetenskapliga studier antyder att mellan 70 och 96 procent av ungdomar som vårdas vid institution kan ha upplevt olika trauman.Av de granskade studierna framkommer att det är vanligt att trauman skett inom familjen i form av till exempel fysisk misshandel och sexuella övergrepp. Men det framkommer även att många institutionsvårdade ungdomar har upplevt våldsbrott "ute på stan". Andra exempel på trauman kan vara att ha bevittnat när andra människor utsätts för skrämmande händelser eller att ha upplevt svåra separationer inom familjen.När barn och ungdomar har utsatts för trauman, särskilt långvariga och upprepade sådana, kan det störa stora delar av deras utveckling. Det kan till exempel synas som en sänkt funktionsförmåga inom många olika livsområden som skolgång, kamratrelationer och identitetsutveckling.Det saknas kunskap om effektiv behandling för traumatiserade ungdomar inom institutionsvård. Det finns dock internationell samstämmighet om att första steget i traumabehandling bör vara insatser som minskar symptom på trauma och verkar stabiliserande på tillvaron. Rapporten ger förslag på hur SiS kan arbeta vidare med att utveckla kunskap om hur ungdomar som visar tecken på traumatisering kan bemötas och erbjudas insatser utifrån sina specifika behov.
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| 16. |
- Jiao, Hong, et al.
(författare)
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Genetic Association and Gene Expression Analysis Identify FGFR1 as a New Susceptibility Gene for Human Obesity
- 2011
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 96:6, s. E962-E966
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Tidskriftsartikel (refereegranskat)abstract
- Context: Previous studies suggest a role for fibroblast growth factor receptor 1 (FGFR1) in the regulation of energy balance. Objective: Our objective was to investigate whether FGFR1 is an obesity gene by genetic association and functional studies. Design: The study was designed to genotype common FGFR1 single-nucleotide polymorphisms (SNP) in large cohorts, confirm significant results in additional cohorts, and measure FGFR1 expression in human adipose tissue and in rodent hypothalamus. Setting: General community and referral centers for specialized care was the setting for the study. Participants: We genotyped FGFR1 SNP in 2438 obese and 2115 lean adults and 985 obese and 532 population-based children. Results were confirmed in 928 obese and 2738 population-based adults and 487 obese and 441 lean children. Abdominal sc adipose tissue was investigated in 202 subjects. We also investigated diet-induced, obese fasting, and fed rats. Main Outcome Measures: We analyzed the association between FGFR1 SNP and obesity. In secondary analyses, we related adipose FGFR1 expression to genotype, obesity, and degree of fat cell differentiation and related hypothalamic FGFR1 to energy balance. Results: FGFR1 rs7012413*T was nominally associated with obesity in all four cohorts; metaanalysis odds ratio = 1.17 (95% confidence interval = 1.10-1.25), and P = 1.8 x 10(-6), which was P = 7.0 x 10(-8) in the recessive model. rs7012413*T was associated with FGFR1 expression in adipose tissue (P < 0.0001). In this organ, but not in skeletal muscle, FGFR1 mRNA (P < 0.0001) and protein (P < 0.05) were increased in obesity. In rats, hypothalamic expression of FGFR1 declined after fasting (P < ]0.001) and increased after diet-induced obesity (P < 0.05). Conclusions: FGFR1 is a novel obesity gene that may promote obesity by influencing adipose tissue and the hypothalamic control of appetite.
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| 17. |
- Karlsson-Lindahl, Linda, 1972, et al.
(författare)
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Heparanase affects food intake and regulates energy balance in mice.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.
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| 18. |
- Speliotes, Elizabeth K, et al.
(författare)
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Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.
- 2011
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n=880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.
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| 19. |
- Synnergren, Jane, et al.
(författare)
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Global transcriptional profiling reveals similarities and differences between human stem cell-derived cardiomyocyte clusters and heart tissue
- 2012
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 44:4, s. 245-258
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Tidskriftsartikel (refereegranskat)abstract
- It is now well documented that human embryonic stem cells (hESCs) can differentiate into functional cardiomyocytes. These cells constitute a promising source of material for use in drug development, toxicity testing, and regenerative medicine. To assess their utility as replacement or complement to existing models, extensive phenotypic characterization of the cells is required. In the present study, we used microarrays and analyzed the global transcription of hESC-derived cardiomyocyte clusters (CMCs) and determined similarities as well as differences compared with reference samples from fetal and adult heart tissue. In addition, we performed a focused analysis of the expression of cardiac ion channels and genes involved in the Ca2+-handling machinery, which in previous studies have been shown to be immature in stem cell-derived cardiomyocytes. Our results show that hESC-derived CMCs, on a global level, have a highly similar gene expression profile compared with human heart tissue, and their transcriptional phenotype was more similar to fetal than to adult heart. Despite the high similarity to heart tissue, a number of significantly differentially expressed genes were identified, providing some clues toward understanding the molecular difference between in vivo sourced tissue and stem cell derivatives generated in vitro. Interestingly, some of the cardiacrelated ion channels and Ca2+-handling genes showed differential expression between the CMCs and heart tissues. These genes may represent candidates for future genetic engineering to create hESC-derived CMCs that better mimic the phenotype of the cardiomyocytes present in the adult human heart.
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