| 1. |
- Gretarsdottir, Solveig, et al.
(författare)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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| 2. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 3. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 4. |
- Helgadottir, Anna, et al.
(författare)
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Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
- 2012
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:8, s. 722-729
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation
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| 5. |
- Hilmarsdóttir, Bylgja, et al.
(författare)
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MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis.
- 2015
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Ingår i: Developmental Biology. - : Elsevier BV. - 1095-564X .- 0012-1606. ; 403:2, s. 150-161
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Tidskriftsartikel (refereegranskat)abstract
- The epithelial compartment of the breast contains two lineages, the luminal- and the myoepithelial cells. D492 is a breast epithelial cell line with stem cell properties that forms branching epithelial structures in 3D culture with both luminal- and myoepithelial differentiation. We have recently shown that D492 undergo epithelial to mesenchymal transition (EMT) when co-cultured with endothelial cells. This 3D co-culture model allows critical analysis of breast epithelial lineage development and EMT. In this study, we compared the microRNA (miR) expression profiles for D492 and its mesenchymal-derivative D492M. Suppression of the miR-200 family in D492M was among the most profound changes observed. Exogenous expression of miR-200c-141 in D492M reversed the EMT phenotype resulting in gain of luminal but not myoepithelial differentiation. In contrast, forced expression of ∆Np63 in D492M restored the myoepithelial phenotype only. Co-expression of miR-200c-141 and ∆Np63 in D492M restored the branching morphogenesis in 3D culture underlining the requirement for both luminal and myoepithelial elements for obtaining full branching morphogenesis in breast epithelium. Introduction of a miR-200c-141 construct in both D492 and D492M resulted in resistance to endothelial induced EMT. In conclusion, our data suggests that expression of miR-200c-141 and ∆Np63 in D492M can reverse EMT resulting in luminal- and myoepithelial differentiation, respectively, demonstrating the importance of these molecules in epithelial integrity in the human breast.
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| 6. |
- Immerstrand, Charlotte, et al.
(författare)
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Conjugated-polymer micro- and milliactuators for biological applications
- 2002
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Ingår i: MRS bulletin. - : Springer Science and Business Media LLC. - 0883-7694 .- 1938-1425. ; 27:6, s. 461-464
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Tidskriftsartikel (refereegranskat)abstract
- The development of new conjugated-polymer tools for the study of the biological realm, and for use in a clinical setting, is reviewed in this article. Conjugated-polymer actuators, based on the changes of volume of the active conjugated polymer during redox transformation, can be used in electrolytes employed in cell-culture media and in biological fluids such as blood, plasma, and urine. Actuators ranging in size from 10 μm to 100 μm suitable for building structures to manipulate single cells are produced with photolithographic techniques. Larger actuators may be used for the manipulation of blood vessels and biological tissue.
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| 7. |
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| 8. |
- Loxbo, Karl, 1975-
(författare)
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Bakom socialdemokraternas beslut. : - från 1950-talets ATP-strid till 1990-talets pensionsuppgörelse
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In 1959, the Swedish Social Democratic Party prevailed over the bourgeois parties in the great battle for supplementary pensions (ATP). In the 1990’s, however, the party leadership decided to abolish the ATP in close cooperation with the bourgeois parties. The thesis poses the following question: “What prospects did the Social Democratic leadership have to gain support for the ATP-reform in the 1950’s, and then for the quite dissimilar pension reform in the 1990’s, and how can differences between these prospects be explained?” In order to explain the kind of party change pointed out in the problem statement, this thesis proposes a theoretical perspective that focuses on the tension between different roles played by the party leadership on different arenas. The hypothesis, that is tested in the thesis, is that early decisions create different constrains for future decisions on different arenas. The thesis has two main conclusions. The first conclusion is that the decision to implement the generous ATP-system in the 1950’s in practice laid the ground for the subsequent abolishment of that same system in the 1990’s. The second conclusion is that the pragmatism, always displayed on the parliamentary arena, has not been visible on the electoral arena or on the party arena. The party leadership plays different roles on different arenas, and over time these different roles have become hard, if not impossible, to combine. The result of this was that decisions on the parliamentary arena were decoupled from messages and rhetoric about these decisions on the party arena, and on the electoral arena. The pension reform in the 1990’s was quite a different decision compared to the popular introduction of the ATP-system. Both of these decisions, however, were attempts by the party leadership to maximize support on each arena. The possibilities for succeeding in this venture were greatly reduced in the 1990’s. Instead of one party striving for one goal, Swedish Social Democracy in the 1990’s appeared as two or three parties, with different objectives and goals.
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| 9. |
- Munch, Andreas, et al.
(författare)
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Low levels of bile acids increase bacterial uptake in colonic biopsies from patients with collagenous colitis in remission
- 2011
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Ingår i: ALIMENTARY PHARMACOLOGY and THERAPEUTICS. - : Blackwell Publishing Ltd. - 0269-2813. ; 33:8, s. 954-960
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Tidskriftsartikel (refereegranskat)abstract
- Pandgt;Background Patients with collagenous colitis have an impaired mucosal barrier. Moreover, collagenous colitis is associated with bile acid malabsorption. Bile acids can increase bacterial mucosal uptake in humans. Mucosal barrier function was investigated by exposing colonic biopsies to chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA) in Ussing chamber experiments. Aim To find if low levels of bile acids increase bacterial uptake in colonic biopsies from collagenous colitis patients. Methods The study comprised 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease and 10 examined in clinical remission resulting from treatment with 6 mg budesonide); eight healthy individuals undergoing screening colonoscopy served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), potential difference, trans-epithelial resistance and transmucosal passage of Escherichia coli K12 after adding 100 mu mol/L CDCA or DCA. Results When adding 100 mu mol/L CDCA or DCA, bacterial uptake increased fourfold in biopsies of patients in remission; CDCA 6.5 units [2.5-9.8] and DCA 6.2 units [2.1-22] (median [IQR]), compared with uptake in biopsies without added bile acids 1.6 units [1.1-3] (P = 0.004 and P = 0.01 respectively). In active disease and in patients in remission due to budesonide treatment, bile acids did not affect bacterial uptake. Confocal microscopy revealed trans-epithelial passage of E. coli K12 within 30 min. Conclusions Low concentrations of dihydroxy-bile acids exacerbate mucosal barrier dysfunction in colonic biopsies of patients with collagenous colitis in remission. This allows a substantially increased bacterial uptake, which may contribute to recurrence of inflammation.
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| 10. |
- Münch, Andreas, et al.
(författare)
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Physiological levels of bile acids increase bacterial uptake in colonic biopsies of collagenous colitis patients in remission
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Patients with collagenous colitis (CC) have an impaired mucosal barrier. Moreover CC is associated with bile acid malabsorption. Bile acids may increase bacterial mucosal uptake in humans. To elucidate the possible role of bile acids in CC pathophysiology, the mucosal barrier function was investigated by exposing colonic biopsies to physiological concentrations of chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA) in Ussing chamber experiments. Patients/Interventions: The study included 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease, and 8 of these again after 6 weeks budesonide treatment); 8 healthy individuals undergoing screening colonoscopy served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short circuit current (Isc), transepithelial resistance (TER), and transmucosal passage of chemically killed E. coli K12 after addition of 100 μmol/l CDCA or DCA. The biopsies were further investigated with confocal microscopy to asses bacterial transepithelial passage routes. Results: By adding 100μmol/l CDCA or DCA the bacterial uptake was increased by 4-fold in biopsies of patients in remission; CDCA 6.5 units [2.5-9.8] and DCA 6.2 units [2.1-22] (median [IQR]), compared with uptake in biopsies without added bile acids 1.6 units [1.1-3]; (p=0.004 and p=0.01, respectively). In active disease and in patients in remission on budesonide, bile acids had no effect on bacterial uptake. Isc and TER were unaffected by the bile acids at 100μmol/l in all groups. Confocal microscopy demonstrated transepithelial passage of E.coli K12 via the paracellular route. Conclusions: Physiological concentrations of dihydroxy-bile acids augment mucosal barrier dysfunction in colonic biopsies of patients with CC in remission. This leads to a substantially increased bacterial uptake that may contribute to relapse of inflammation. Budesonide seems to counteract the bile acid-induced mucosal impairment.
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