| 21. |
- Perry, John R. B., et al.
(författare)
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Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m(2)) compared to obese cases (BMI >= 30 Kg/m(2)). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m(2)) or 4,123 obese cases (BMI >= 30 kg/m(2)), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P = 8.4610 29, OR = 1.13 [95% CI 1.09-1.18]), and this association was stronger than that in obese cases (P = 0.04, OR = 1.03 [95% CI 1.00-1.06]). A variant in HMG20A-previously identified in South Asians but not Europeans-was associated with type 2 diabetes in obese cases (P = 1.3 x 10(-8), OR= 1.11 [95% CI 1.07-1.15]), although this association was not significantly stronger than that in lean cases (P = 0.02, OR = 1.09 [95% CI 1.02-1.17]). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P = 0.0002). In the lean analysis, we observed a weighted per-risk allele OR = 1.13 [95% CI 1.10-1.17], P = 3.2 x 10(-14). This was larger than the same model fitted in the obese analysis where the OR = 1.06 [95% CI 1.05-1.08], P = 2.2 x 10(-16). This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes.
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| 22. |
- Scott, Robert A., et al.
(författare)
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An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
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Tidskriftsartikel (refereegranskat)abstract
- To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
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| 23. |
- Siggeirsdottir, Kristin, et al.
(författare)
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Effect of vertebral fractures on function, quality of life and hospitalisation the AGES-Reykjavik study
- 2012
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 1468-2834 .- 0002-0729. ; 41:3, s. 351-357
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Tidskriftsartikel (refereegranskat)abstract
- Objective: assess the effect of clinical vertebral and other osteoporotic fractures on function and the subsequent risk of hospitalisation. Design: individuals from the prospective population-based cohort study Age, Gene/Environment Susceptibility (AGES)-Reykjavik study were examined between 2002 and 2006 and followed up for 5.4 years. Subjects: a total of 5,764 individuals, 57.7% women, born 1907-35, mean age 77. Method: four groups with a verified fracture status were used; vertebral fractures, other osteoporotic fractures excluding vertebral, non-osteoporotic fractures and not-fractured were compared and analysed for the effect on mobility, strength, QoL, ADL, co-morbidity and hospitalisation. Results: worst performance on functional tests was in the vertebral fracture group for women (P < 0.0001) and the other osteoporotic fractures group for men (P < 0.05). Both vertebral and other osteoporotic fractures, showed an increased risk of hospitalisation, HR = 1.4 (95% CI: 1.3-1.7) and 1.2 (95% CI: 1.1-1.2) respectively (P < 0.0001). Individuals with vertebral fractures had 50% (P < 0.0001) longer hospitalisation than not-fractured and 33% (P < 0.002) longer than the other osteoporotic fractures group. Conclusion: individuals with a history of clinical vertebral fracture seem to carry the greatest health burden compared with other fracture groups, emphasising the attention which should be given to those individuals.
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| 24. |
- Siggeirsdottir, Kristin, et al.
(författare)
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Inaccuracy in self-report of fractures may underestimate association with health outcomes when compared with medical record based fracture registry
- 2007
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 22:9, s. 631-639
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Tidskriftsartikel (refereegranskat)abstract
- Introduction and objective Misreporting fractures in questionnaires is known. However, the effect of misreporting on the association of fractures with subsequent health outcomes has not been examined. Methods Data from a fracture registry (FR) developed from an extensive review of radiographic and medical records were related to self-report of fracture for 2,255 participants from the AGES Reykjavik Study. This data was used to determine false negative and false positive rates of self-reported fractures, correlates of misreporting, and the potential effect of the misreporting on estimates of health outcomes following fractures. Results In women, the false positive rate decreased with age as the false negative rate increased with no clear trend with age in men. Kappa values for agreement between FR and self-report were generally higher in women than men with the best agreement for forearm fracture (men 0.64 and women 0.82) and the least for rib (men 0.28 and women 0.25). Impaired cognition was a major factor associated with discordant answers between FR and self-report, OR 1.7 (95% CI: 1.3-2.1) (P < 0.0001). We estimated the effect of misreporting on health after fracture by comparison of the association of the self-report of fracture and fracture from the FR, adjusting for those factors associated with discordance. The weighted attenuation factor measured by mobility and muscle strength was 11% (95% CI: 0-24%) when adjusted for age and sex but reduced to 6% (95% CI: -10-22%) when adjusted for cognitive impairment. Conclusion Studies of hip fractures should include an independent ascertainment of fracture but for other fractures this study supports the use of self-report.
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| 25. |
- Sigurdsson, Gunnar, et al.
(författare)
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Bosonic realizations of the colour Heisenberg Lie algebra
- 2006
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Ingår i: Journal of Nonlinear Mathematical Physics. - : Springer Science and Business Media LLC. - 1402-9251 .- 1776-0852. ; 13, s. 110-128
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Tidskriftsartikel (refereegranskat)abstract
- We describe realizations of the colour analogue of the Heisenberg Lie algebra by power series in non-commuting indeterminates satisfying Heisenberg's canonical commutation relations of quantum mechanics. The obtained formulas are used to construct new operator representations of the colour Heisenberg Lie algebra. These representations are shown to be closely connected with some combinatorial identities and functional difference-differential interpolation formulae involving Euler numbers.
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| 26. |
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| 27. |
- Sigurdsson, Gunnar, et al.
(författare)
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Graded quasi-Lie algebras of Witt type
- 2006
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Ingår i: Czechoslovak Journal of Physics. - : Springer Science and Business Media LLC. - 0011-4626 .- 1572-9486. ; 56:10-11, s. 1287-1291
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we introduce a new class of graded algebras called quasi-Lie algebras of Witt type. These algebras can be seen as a generalization of other Witt-type algebras like Lie algebras of Witt type and their colored version, Lie color algebras of Witt type.
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| 28. |
- Sigurdsson, Gunnar, et al.
(författare)
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Lie Color and Hom-Lie Algebras of Witt Type and Their Central Extensions
- 2009
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Ingår i: GENERALIZED LIE THEORY IN MATHEMATICS, PHYSICS AND BEYOND. - BERLIN : SPRINGER-VERLAG BERLIN. - 9783540853312 - 9783540853329 ; , s. 247-255
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Konferensbidrag (refereegranskat)abstract
- In this article, two classes of Gamma-graded Witt-type algebras, Lie color and hom-Lie algebras of Witt type, are considered. These algebras can be seen as generalizations of Lie algebras of Witt type. One-dimensional central extensions of Lie color and hom-Lie algebras of Witt type are investigated.
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| 29. |
- Sigurdsson, Gunnar, et al.
(författare)
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Matrix bosonic realizations of a Lie colour algebra with three generators and five relations of Heisenberg Lie type
- 2009
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Ingår i: Journal of Generalized Lie Theory and Applications. - 1736-5279 .- 1736-4337. ; 3:4, s. 329-340
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Tidskriftsartikel (refereegranskat)abstract
- We describe realizations of a Lie colour algebra with three generators and five relations by matrices of power series in noncommuting indeterminates satisfying Heisenberg's canonical commutation relation of quantum mechanics. The obtained formulas are used to construct new operator representations of this Lie colour algebra using canonical representation of the Heisenberg commutation relation and creation and annihilation operators of the quantum mechanical harmonic oscillator.
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| 30. |
- Sigurðsson, Halldor Armann, et al.
(författare)
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Icelandic Dative Intervention
- 2008
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Ingår i: Agreement Restrictions. ; , s. 251-279
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Bokkapitel (refereegranskat)
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