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

共 29 条

[1]

[Anonymous], [No title captured]

[2] A genome-wide association study implicates diacylglycerol kinase η (DGKH) and several other genes in the etiology of bipolar disorder [J].

Baum, A. E. ;

Akula, N. ;

Cabanero, M. ;

Cardona, I. ;

Corona, W. ;

Klemens, B. ;

Schulze, T. G. ;

Cichon, S. ;

Rietschel, M. ;

Noethen, M. M. ;

Georgi, A. ;

Schumacher, J. ;

Schwarz, M. ;

Abou Jamra, R. ;

Hoefels, S. ;

Propping, P. ;

Satagopan, J. ;

Detera-Wadleigh, S. D. ;

Hardy, J. ;

McMahon, F. J. .

MOLECULAR PSYCHIATRY, 2008, 13 (02) :197-207

[3] A POLYMORPHIC LOCUS NEAR THE HUMAN INSULIN GENE IS ASSOCIATED WITH INSULIN-DEPENDENT DIABETES-MELLITUS [J].

BELL, GI ;

HORITA, S ;

KARAM, JH .

DIABETES, 1984, 33 (02) :176-183

[4] Joint effects of HLA, INS, PTPN22 and CTLA4 genes on the risk of type 1 diabetes [J].

Bjornvold, M. ;

Undlien, D. E. ;

Joner, G. ;

Dahl-Jorgensen, K. ;

Njolstad, P. R. ;

Akselsen, H. E. ;

Gervin, K. ;

Ronningen, K. S. ;

Stene, L. C. .

DIABETOLOGIA, 2008, 51 (04) :589-596

[5] A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes [J].

Bottini, N ;

Musumeci, L ;

Alonso, A ;

Rahmouni, S ;

Nika, K ;

Rostamkhani, M ;

MacMurray, J ;

Meloni, GF ;

Lucarelli, P ;

Pellecchia, M ;

Eisenbarth, GS ;

Comings, D ;

Mustelin, T .

NATURE GENETICS, 2004, 36 (04) :337-338

[6] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[7] Detecting disease associations due to linkage disequilibrium using haplotype tags: A class of tests and the determinants of statistical power [J].

Chapman, JM ;

Cooper, JD ;

Todd, JA ;

Clayton, DG .

HUMAN HEREDITY, 2003, 56 (1-3) :18-31

[8] Testing for association on the X chromosome [J].

Clayton, David .

BIOSTATISTICS, 2008, 9 (04) :593-600

[9] A human type 1 diabetes susceptibility locus maps to chromosome 21q22.3 [J].

Concannon, Patrick ;

Onengut-Gumuscu, Suna ;

Todd, John A. ;

Smyth, Deborah J. ;

Pociot, Flemming ;

Bergholdt, Regine ;

Akolkar, Beena ;

Erlich, Henry A. ;

Hilner, Joan E. ;

Julier, Cecile ;

Morahan, Grant ;

Nerup, Jorn ;

Nierras, Concepcion R. ;

Chen, Wei-Min ;

Rich, Stephen S. .

DIABETES, 2008, 57 (10) :2858-2861

[10] Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci [J].

Cooper, Jason D. ;

Smyth, Deborah J. ;

Smiles, Adam M. ;

Plagnol, Vincent ;

Walker, Neil M. ;

Allen, James E. ;

Downes, Kate ;

Barrett, Jeffrey C. ;

Healy, Barry C. ;

Mychaleckyj, Josyf C. ;

Warram, James H. ;

Todd, John A. .

NATURE GENETICS, 2008, 40 (12) :1399-1401

← 1 2 3 →