Common variants at five new loci associated with early-onset inflammatory bowel disease

被引：400

作者：

Imielinski, Marcin ^{[1
]}

Baldassano, Robert N. ^{[2
,3
]}

Griffiths, Anne ^{[4
]}

Russell, Richard K. ^{[5
]}

Annese, Vito ^{[6
]}

Dubinsky, Marla ^{[7
,8
]}

Kugathasan, Subra ^{[9
,10
]}

Bradfield, Jonathan P. ^{[1
]}

Walters, Thomas D. ^{[4
]}

Sleiman, Patrick ^{[1
]}

Kim, Cecilia E. ^{[1
]}

Muise, Aleixo ^{[4
]}

Wang, Kai ^{[1
]}

Glessner, Joseph T. ^{[1
]}

Saeed, Shehzad ^{[11
]}

Zhang, Haitao ^{[1
]}

Frackelton, Edward C. ^{[1
]}

Hou, Cuiping ^{[1
]}

Flory, James H. ^{[1
]}

Otieno, George ^{[1
]}

Chiavacci, Rosetta M. ^{[1
]}

Grundmeier, Robert ^{[2
,12
]}

Castro, Massimo ^{[13
]}

Latiano, Anna ^{[13
]}

Dallapiccola, Bruno ^{[14
]}

Stempak, Joanne ^{[15
]}

Abrams, Debra J. ^{[3
]}

Taylor, Kent ^{[8
]}

McGovern, Dermot ^{[8
]}

Heyman, Melvin B. ^{[16
]}

Ferry, George D. ^{[17
]}

Kirschner, Barbara ^{[18
]}

Lee, Jessica ^{[19
]}

Essers, Jonah ^{[19
]}

Grand, Richard ^{[19
]}

Stephens, Michael ^{[20
]}

Levine, Arie ^{[21
]}

Piccoli, David ^{[2
,3
]}

Van Limbergen, Johan ^{[22
]}

Cucchiara, Salvatore ^{[23
]}

Monos, Dimitri S. ^{[24
]}

Guthery, Stephen L. ^{[25
,26
]}

Denson, Lee ^{[27
]}

Wilson, David C. ^{[28
]}

Grant, Struan F. A. ^{[1
,2
,29
]}

Daly, Mark ^{[30
]}

Silverberg, Mark S. ^{[15
]}

Satsangi, Jack ^{[22
]}

Hakonarson, Hakon ^{[1
,2
,29
]}

机构：

[1] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

[3] Childrens Hosp Philadelphia, Div Gastroenterol, Philadelphia, PA 19104 USA

[4] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[5] Royal Hosp Sick Children, Glasgow G3 8SJ, Lanark, Scotland

[6] CSS, IRCCS, Dept Med Sci, Gastroenterol Unit, San Giovanni Rotondo, Italy

[7] Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA

[8] Cedars Sinai Med Ctr, Dept Common Dis Genet, Los Angeles, CA 90048 USA

[9] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA

[10] Childrens Hlth Care Atlanta, Atlanta, GA USA

[11] Univ Alabama, Dept Pediat, Birmingham, AL USA

[12] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA

[13] Bambino Gesu Pediat Hosp, Gastroenterol Unit, Rome, Italy

[14] Univ Roma La Sapienza, Mendel Inst, IRCCS, CSS Hosp, San Giovanni Rotondo, Italy

[15] Univ Toronto, Mt Sinai Hosp, Ctr Inflammatory Bowel Dis, Toronto, ON M5G 1X5, Canada

[16] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

[17] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[18] Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA

[19] Childrens Hosp, Div Gastroenterol, Boston, MA 02115 USA

[20] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA

[21] Tel Aviv Univ, Wolfson Med Ctr, Pediat Gastroenterol Unit, IL-69978 Tel Aviv, Israel

[22] Univ Edinburgh, Western Gen Hosp, Sch Mol & Clin Med, Div Med Sci,Gastrointestinal Unit, Edinburgh, Midlothian, Scotland

[23] Univ Roma La Sapienza, Pediat Gastroenterol & Liver Unit, Rome, Italy

[24] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA

[25] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA

[26] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA

[27] Cincinnati Childrens Hosp, Med Ctr, Div Gastroenterol, Ctr Inflammatory Bowel Dis, Cincinnati, OH USA

[28] Royal Hosp Sick Children, Edinburgh EH9 1LF, Midlothian, Scotland

[29] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[30] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 12期

基金：

英国惠康基金; 英国医学研究理事会; 加拿大健康研究院;

关键词：

GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; SEQUENCE VARIANTS; GENE; EXPRESSION; CONTRIBUTE; AUTOPHAGY; MULTIPLE; HISTORY;

D O I：

10.1038/ng.489

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD1. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

引用

页码：1335 / U107

页数：8

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