Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study

被引：315

作者：

Silverberg, Mark S. ^{[1
]}

Cho, Judy H. ^{[2
,3
]}

Rioux, John D. ^{[4
,5
]}

McGovern, Dermot P. B. ^{[6
]}

Wu, Jing ^{[7
]}

Annese, Vito ^{[8
]}

Achkar, Jean-Paul ^{[9
]}

Goyette, Philippe ^{[4
,5
]}

Scott, Regan ^{[10
]}

Xu, Wei ^{[11
]}

Barmada, M. Michael ^{[12
]}

Klei, Lambertus ^{[13
]}

Daly, Mark J. ^{[14
]}

Abraham, Clara ^{[4
]}

Bayless, Theodore M. ^{[15
]}

Bossa, Fabrizio ^{[8
]}

Griffiths, Anne M. ^{[16
]}

Ippoliti, Andrew F. ^{[6
]}

Lahaie, Raymond G. ^{[17
,18
]}

Latiano, Anna ^{[8
]}

Pare, Pierre ^{[19
,20
]}

Proctor, Deborah D. ^{[2
]}

Regueiro, Miguel D. ^{[10
]}

Steinhart, A. Hillary ^{[1
]}

Targan, Stephan R. ^{[6
]}

Schumm, L. Philip ^{[21
]}

Kistner, Emily O. ^{[21
]}

Lee, Annette T. ^{[22
]}

Gregersen, Peter K. ^{[22
]}

Rotter, Jerome I. ^{[6
,19
]}

Brant, Steven R. ^{[15
,24
]}

Taylor, Kent D. ^{[6
,23
]}

Roeder, Kathryn ^{[7
]}

Duerr, Richard H. ^{[10
,12
]}

机构：

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

[2] Yale Univ, Sect Digest Dis, Dept Med, New Haven, CT 06520 USA

[3] Yale Univ, Dept Genet, New Haven, CT 06520 USA

[4] Univ Montreal, Montreal, PQ H1T 1C8, Canada

[5] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada

[6] Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90048 USA

[7] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA

[8] IRCCS CSS Hosp, I-71013 San Giovanni Rotondo, FG, Italy

[9] Cleveland Clin, Inst Digest Dis, Cleveland, OH 44195 USA

[10] Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Sch Med,UPMC PUH, Pittsburgh, PA 15213 USA

[11] Univ Toronto, Princess Margaret Hosp, Dept Publ Hlth Sci, Toronto, ON M5G 2M9, Canada

[12] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA

[13] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA

[14] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA

[15] Johns Hopkins Univ, Sch Med, Dept Med, Harvey M & Lyn P Meyerhoff Infammatory Bowel Dis, Baltimore, MD 21287 USA

[16] Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada

[17] Univ Montreal, Dept Med, Montreal, PQ H2X 3J4, Canada

[18] CHUM, Hop St Luc, Montreal, PQ H2X 3J4, Canada

[19] Univ Laval, Dept Med, Div Gastroenterol, Quebec City, PQ G1K 7P4, Canada

[20] CHAUQ Hop St Sacrement, Ste Foy, PQ G1S 4L8, Canada

[21] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA

[22] Feinstein Inst Med Res, Manhasset, NY 11030 USA

[23] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[24] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21231 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 02期

基金：

美国国家卫生研究院;

关键词：

INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; SEQUENCE VARIANTS; GENE; EXPRESSION; MULTIPLE; PATHOGENESIS; REPLICATION; CONTRIBUTE;

D O I：

10.1038/ng.275

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29).

引用

页码：216 / 220

页数：5

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