| 1. |
- Sigurdsson, Snaevar, et al.
(author)
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A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5
- 2008
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 17:18, s. 2868-2876
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is the prototype autoimmune disease where genes regulated by type I interferon (IFN) are over-expressed and contribute to the disease pathogenesis. Because signal transducer and activator of transcription 4 (STAT4) plays a key role in the type I IFN receptor signaling, we performed a candidate gene study of a comprehensive set of single nucleotide polymorphism (SNPs) in STAT4 in Swedish patients with SLE. We found that 10 out of 53 analyzed SNPs in STAT4 were associated with SLE, with the strongest signal of association (P = 7.1 x 10(-8)) for two perfectly linked SNPs rs10181656 and rs7582694. The risk alleles of these 10 SNPs form a common risk haplotype for SLE (P = 1.7 x 10(-5)). According to conditional logistic regression analysis the SNP rs10181656 or rs7582694 accounts for all of the observed association signal. By quantitative analysis of the allelic expression of STAT4 we found that the risk allele of STAT4 was over-expressed in primary human cells of mesenchymal origin, but not in B-cells, and that the risk allele of STAT4 was over-expressed (P = 8.4 x 10(-5)) in cells carrying the risk haplotype for SLE compared with cells with a non-risk haplotype. The risk allele of the SNP rs7582694 in STAT4 correlated to production of anti-dsDNA (double-stranded DNA) antibodies and displayed a multiplicatively increased, 1.82-fold risk of SLE with two independent risk alleles of the IRF5 (interferon regulatory factor 5) gene.
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| 2. |
- Sigurdsson, Snaevar, et al.
(author)
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Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for systemic lupus erythematosus
- 2008
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 17:6, s. 872-881
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Journal article (peer-reviewed)abstract
- We analyzed a comprehensive set of single-nucleotide polymorphisms (SNPs) and length polymorphisms in the interferon regulatory factor 5 (IRF5) gene for their association with the autoimmune disease systemic lupus erythematosus (SLE) in 485 Swedish patients and 563 controls. We found 16 SNPs and two length polymorphisms that display association with SLE (P < 0.0005, OR > 1.4). Using a Bayesian model selection and averaging approach we identified parsimonious models with exactly two variants of IRF5 that are independently associated with SLE. The variants of IRF5 with the highest posterior probabilities (1.00 and 0.71, respectively) of being causal in SLE are a SNP (rs10488631) located 3' of IRF5, and a novel CGGGG insertion-deletion (indel) polymorphism located 64 bp upstream of the first untranslated exon (exon 1A) of IRF5. The CGGGG indel explains the association signal from multiple SNPs in the IRF5 gene, including rs2004640, rs10954213 and rs729302 previously considered to be causal variants in SLE. The CGGGG indel contains three or four repeats of the sequence CGGGG with the longer allele containing an additional SP1 binding site as the risk allele for SLE. Using electrophoretic mobility shift assays we show increased binding of protein to the risk allele of the CGGGG indel and using a minigene reporter assay we show increased expression of IRF5 mRNA from a promoter containing this allele. Increased expression of IRF5 protein was observed in peripheral blood mononuclear cells from SLE patients carrying the risk allele of the CGGGG indel. We have found that the same IRF5 allele also confers risk for inflammatory bowel diseases and multiple sclerosis, suggesting a general role for IRF5 in autoimmune diseases.
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| 3. |
- Helgadottir, Anna, et al.
(author)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
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Journal article (peer-reviewed)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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| 4. |
- Larsson, Daniel, et al.
(author)
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On some almost quadratic algebras coming from twisted derivations
- 2006
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In: Journal of Nonlinear Mathematical Physics. - 1402-9251 .- 1776-0852. ; 13, s. 76-86
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Journal article (peer-reviewed)abstract
- This paper explores the quasi-deformation scheme devised in [1, 3] as applied to the simple Lie algebra sl(2)(F) for specific choices of the involved parameters and underlying algebras. One of the main points of this method is that the quasi-deformed algebra comes endowed with a canonical twisted Jacobi identity. We show in the present article that when the quasi-deformation method is applied to sl(2)(F) one obtains multiparameter families of almost quadratic algebras, and by choosing parameters suitably, sl(2)(F) is quasi-deformed into three-dimensional and four-dimensional Lie algebras and algebras closely resembling Lie superalgebras and colour Lie algebras, this being in stark contrast to the classical deformation schemes where sl(2)(F) is rigid.
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| 5. |
- Larsson, Daniel, et al.
(author)
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On some almost quadratic algebras coming from twisted derivations
- 2006
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In: Journal of Nonlinear Mathematical Physics. - : Springer Science and Business Media LLC. - 1402-9251 .- 1776-0852. ; 13, s. 76-86
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Journal article (peer-reviewed)abstract
- This paper explores the quasi-deformation scheme devised in [1, 3] as applied to the simple Lie algebra sl(2)(F) for specific choices of the involved parameters and underlying algebras. One of the main points of this method is that the quasi-deformed algebra comes endowed with a canonical twisted Jacobi identity. We show in the present article that when the quasi-deformation method is applied to sl(2)(F) one obtains multiparameter families of almost quadratic algebras, and by choosing parameters suitably, sl(2)(F) is quasi-deformed into three-dimensional and four-dimensional Lie algebras and algebras closely resembling Lie superalgebras and colour Lie algebras, this being in stark contrast to the classical deformation schemes where sl(2)(F) is rigid.
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| 6. |
- Larsson, Daniel, et al.
(author)
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Quasi-Lie deformations on the algebra F[t]/(tn)
- 2008
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In: Journal of Generalized Lie Theory and Applications. - 1736-5279 .- 1736-4337. ; 2:3, s. 201-205
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Journal article (peer-reviewed)abstract
- This paper explores the quasi-deformation scheme devised by Hartwig, Larsson and Silvestrov as applied to the simple Lie algebra sl2(F). One of the main points of this method is that the quasi-deformed algebra comes endowed with a canonical twisted Jacobi identity. We show in the present article that when the quasi-deformation method is applied to sl2(F) via representations by twisted derivations on the algebra F[t]/(tN) one obtains interesting new multi-parameter families of almost quadratic algebras.
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| 7. |
- Siggeirsdottir, Kristin, et al.
(author)
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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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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 22:9, s. 631-639
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Journal article (peer-reviewed)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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| 8. |
- Sigurdsson, Gunnar, et al.
(author)
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Bosonic realizations of the colour Heisenberg Lie algebra
- 2006
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In: Journal of Nonlinear Mathematical Physics. - : Springer Science and Business Media LLC. - 1402-9251 .- 1776-0852. ; 13, s. 110-128
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Journal article (peer-reviewed)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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| 9. |
- Sigurdsson, Gunnar, et al.
(author)
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Graded quasi-Lie algebras of Witt type
- 2006
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In: Czechoslovak Journal of Physics. - : Springer Science and Business Media LLC. - 0011-4626 .- 1572-9486. ; 56:10-11, s. 1287-1291
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Journal article (peer-reviewed)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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| 10. |
- Sigurdsson, Gunnar, et al.
(author)
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Lie Color and Hom-Lie Algebras of Witt Type and Their Central Extensions
- 2009
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In: GENERALIZED LIE THEORY IN MATHEMATICS, PHYSICS AND BEYOND. - BERLIN : SPRINGER-VERLAG BERLIN. - 9783540853312 - 9783540853329 ; , s. 247-255
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Conference paper (peer-reviewed)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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| 11. |
- Sigurdsson, Gunnar, et al.
(author)
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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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In: Journal of Generalized Lie Theory and Applications. - 1736-5279 .- 1736-4337. ; 3:4, s. 329-340
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Journal article (peer-reviewed)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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| 12. |
- Sigurðsson, Halldor Armann, et al.
(author)
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Icelandic Dative Intervention
- 2008
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In: Agreement Restrictions. ; , s. 251-279
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Book chapter (peer-reviewed)
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| 13. |
- Sigurdsson, Snaevar, et al.
(author)
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Association of a Haplotype in the Promoter Region of the Interferon Regulatory Factor 5 Gene With Rheumatoid Arthritis
- 2007
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 56:7, s. 2202-2210
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Journal article (peer-reviewed)abstract
- Objective. To determine whether genetic variants of the interferon regulatory factor 5 (IRF-5) and Tyk-2 genes are associated with rheumatoid arthritis (RA). Methods. Five single-nucleotide polymorphisms (SNPs) in IRF5 and 3 SNPs in Tyk2 were analyzed in a Swedish cohort of 1,530 patients with RA and 881 controls. A replication study was performed in a Dutch cohort of 387 patients with RA and 181 controls. All patient sera were tested for the presence of autoantibodies against cyclic citrullinated peptides (anti-CCP). Results. Four of the 5 SNPs located in the 5' region of IRF5 were associated with RA, while no association was observed with the Tyk2 SNPs. The minor alleles of 3 of the IRF5 SNPs, which were in linkage disequilibrium and formed a relatively common haplotype with a frequency of ∼0.33, appeared to confer protection against RA. Although these disease associations were seen in the entire patient group, they were mainly found in RA patients who were negative for anti-CCP. A suggestive association of IRF5 SNPs with anti-CCP-negative RA was also observed in the Dutch cohort. Conclusion. Given the fact that anti-CCP-negative RA differs from anti-CCP-positive RA with respect to genetic and environmental risk factor profiles, our results indicate that genetic variants of IRF5 contribute to a unique disease etiology and pathogenesis in anti-CCP-negative RA.
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| 14. |
- Sigurdsson, S, et al.
(author)
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Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus
- 2005
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 76:3, s. 528-37
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms ( SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control individuals for joint linkage and association with SLE. In two of the genes - the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes - we identified SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P < 10(-7)) with SLE. TYK2 binds to the type I IFN receptor complex and IRF5 is a regulator of type I IFN gene expression. Thus, our results support a disease mechanism in SLE that involves key components of the type I IFN system.
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