Newly identified genetic risk variants for celiac disease related to the immune response

被引：481

作者：

Hunt, Karen A. ^{[1
,3
]}

Zhernakova, Alexandra ^{[2
]}

Turner, Graham ^{[4
]}

Heap, Graham A. R. ^{[1
,3
]}

Franke, Lude ^{[2
]}

Bruinenberg, Marcel ^{[5
,6
]}

Romanos, Jihane ^{[5
,6
]}

Dinesen, Lotte C. ^{[7
]}

Ryan, Anthony W. ^{[4
]}

Panesar, Davinder ^{[1
,3
]}

Gwilliam, Rhian ^{[8
]}

Takeuchi, Fumihiko ^{[8
]}

McLaren, William M. ^{[8
]}

Holmes, Geoffrey K. T. ^{[9
]}

Howdle, Peter D. ^{[10
]}

Walters, Julian R. F. ^{[11
]}

Sanders, David S. ^{[12
,13
]}

Playford, Raymond J. ^{[1
,3
]}

Trynka, Gosia ^{[5
,6
]}

Mulder, Chris J. J. ^{[14
]}

Mearin, M. Luisa ^{[15
,16
]}

Verbeek, Wieke H. M. ^{[14
]}

Trimble, Valerie ^{[4
]}

Stevens, Fiona M. ^{[17
]}

O'Morain, Colm ^{[4
]}

Kennedy, Nicholas P. ^{[4
]}

Kelleher, Dermot ^{[4
]}

Pennington, Daniel J. ^{[1
,3
]}

Strachan, David P. ^{[18
]}

McArdle, Wendy L. ^{[19
]}

Mein, Charles A. ^{[20
,21
]}

Wapenaar, Martin C. ^{[5
,6
]}

Deloukas, Panos ^{[8
]}

McGinnis, Ralph ^{[8
]}

McManus, Ross ^{[4
]}

Wijmenga, Cisca ^{[2
,5
,6
]}

van Heel, David A. ^{[1
,3
]}

机构：

[1] Inst Cell & Mol Sci, Barts E1 2AT, England

[2] Univ Utrecht, Med Ctr, Dept Biomed Genet, Complex Genet Sect, NL-3584 CG Utrecht, Netherlands

[3] London Sch Med & Dent, London E1 2AT, England

[4] Trinity Coll Dublin, Inst Mol Med, Dept Clin Med, Dublin, Ireland

[5] Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands

[6] Univ Groningen, NL-9700 RB Groningen, Netherlands

[7] Univ Oxford, Gastroenterol Unit, Oxford OX3 7BN, England

[8] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[9] Derbyshire Royal Infirm, Dept Gastroenterol, Derby DE1 2QY, England

[10] St James Univ Hosp, Acad Med Unit, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England

[11] Hammersmith Hosp, Univ London Imperial Coll Sci Technol & Med, Gastroenterol Sect, London W12 0HS, England

[12] Royal Hallamshire Hosp, Dept Gastroenterol, Sheffield S10 2JF, S Yorkshire, England

[13] Royal Hallamshire Hosp, Liver Unit, Sheffield S10 2JF, S Yorkshire, England

[14] VU Med Ctr, Dept Gastroenterol, NL-1007 MB Amsterdam, Netherlands

[15] VU Med Ctr, Dept Pediat Gastroenterol, NL-1007 MB Amsterdam, Netherlands

[16] Leiden Univ, Med Ctr, Dept Paediat Gastroenterol, NL-2300 RC Leiden, Netherlands

[17] Natl Univ Ireland, Dept Med, Galway, Ireland

[18] Univ London St Georges Hosp, Div Commun Hlth Sci, London SW17 0RE, England

[19] Univ Bristol, ALSPAC, Bristol BS8 1TQ, Avon, England

[20] London Sch Med & Dent, London EC1M 6BQ, England

[21] Genome Ctr, Barts EC1M 6BQ, England

来源：

NATURE GENETICS | 2008年 / 40卷 / 04期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/ng.102

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways.

引用

页码：395 / 402

页数：8

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