Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes

被引：1311

作者：

Barrett, Jeffrey C. ^{[2
]}

Clayton, David G. ^{[1
,2
]}

Concannon, Patrick ^{[3
]}

Akolkar, Beena ^{[4
]}

Cooper, Jason D. ^{[2
]}

Erlich, Henry A. ^{[5
]}

Julier, Cecile ^{[6
]}

Morahan, Grant ^{[7
,8
]}

Nerup, Jorn ^{[9
,10
]}

Nierras, Concepcion ^{[11
]}

Plagnol, Vincent ^{[2
]}

Pociot, Flemming ^{[9
,10
]}

Schuilenburg, Helen ^{[2
]}

Smyth, Deborah J. ^{[2
]}

Stevens, Helen ^{[2
]}

Todd, John A. ^{[2
]}

Walker, Neil M. ^{[2
]}

Rich, Stephen S. ^{[3
,12
]}

机构：

[1] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22903 USA

[2] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res,Juvenile Diabet Res Fdn, Dept Med Genet,Wellcom Trust Diabet & Inflammat L, Cambridge CB2 2QQ, England

[3] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[4] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA

[5] Roche Mol Syst, Pleasanton, CA USA

[6] INSERM, U958, Ctr Natl Genotypage, Evry, France

[7] Western Australia Inst Med Res, Ctr Diabet Res, Perth, WA, Australia

[8] Univ Western Australia, Med Res Ctr, Perth, WA 6009, Australia

[9] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[10] Hagedorn Res Inst, Gentofte, Denmark

[11] Juvenile Diabet Res Fdn, New York, NY USA

[12] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 06期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

SUSCEPTIBILITY LOCUS; CHROMOSOME; DISEASE; REGION; GENES; HLA; VARIANTS; MELLITUS; PTPN22; TESTS;

D O I：

10.1038/ng.381

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P < 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P < 0.01; overall P < 5 x 10(-8)) and 4 additional regions provided nominal evidence of replication (P < 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.

引用

页码：703 / 707

页数：5

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