Statistical colocalization of genetic risk variants for related autoimmune diseases in the context of common controls

被引：94

作者：

Fortune, Mary D. ^{[1
]}

Guo, Hui ^{[1
,2
]}

Burren, Oliver ^{[1
]}

Schofield, Ellen ^{[1
]}

Walker, Neil M. ^{[1
]}

Ban, Maria ^{[3
]}

Sawcer, Stephen J. ^{[3
]}

Bowes, John ^{[4
,5
]}

Worthington, Jane ^{[4
,5
]}

Barton, Anne ^{[4
,5
]}

Eyre, Steve ^{[4
,5
]}

Todd, John A. ^{[1
]}

Wallace, Chris ^{[1
,6
]}

机构：

[1] Univ Cambridge, Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Dept Med Genet,JDRF Wellcome Trust Diabet & Infla, Cambridge, England

[2] Univ Manchester, Ctr Biostat, Inst Populat Hlth, Manchester, Lancs, England

[3] Addenbrookes Hosp, Univ Neurol Unit, Cambridge, England

[4] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthritis Res UK Ctr Genet & Genom, Ctr Musculoskeletal Res,Inst Inflammat & Repair, Manchester, Lancs, England

[5] Cent Manchester Fdn Trust, Manchester Acad Hlth Sci Ctr, Natl Inst Hlth Res, Manchester Musculoskeletal Biomed Res Unit, Manchester, Lancs, England

[6] Cambridge Inst Publ Hlth, MRC, Biostat Unit, Cambridge, England

来源：

NATURE GENETICS | 2015年 / 47卷 / 07期

基金：

英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院; 芬兰科学院; 瑞典研究理事会;

关键词：

TYPE-2 DIABETES RISK; SUSCEPTIBILITY LOCI; ASSOCIATION SIGNALS; CELIAC-DISEASE; GENOME; ARCHITECTURE; EXPRESSION; INSIGHTS;

D O I：

10.1038/ng.3330

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Determining whether potential causal variants for related diseases are shared can identify overlapping etiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent data sets. Here we extend two colocalization methods to allow for the shared-control design commonly used in comparison of genome-wide association study results across diseases. Our analysis of four autoimmune diseases-type 1 diabetes (T1D), rheumatoid arthritis, celiac disease and multiple sclerosis-identified 90 regions that were associated with at least one disease, 33 (37%) of which were associated with 2 or more disorders. Nevertheless, for 14 of these 33 shared regions, there was evidence that the causal variants differed. We identified new disease associations in 11 regions previously associated with one or more of the other 3 disorders. Four of eight T1D-specific regions contained known type 2 diabetes (T2D) candidate genes (COBL, GLIS3, RNLS and BCAR1), suggesting a shared cellular etiology.

引用

页码：839 / +

页数：9

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