Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease

被引：252

作者：

Kugathasan, Subra ^{[2
,3
,4
,5
]}

Baldassano, Robert N. ^{[6
,7
]}

Bradfield, Jonathan P. ^{[1
]}

Sleiman, Patrick M. A. ^{[1
]}

Imielinski, Marcin ^{[1
]}

Guthery, Stephen L. ^{[8
,9
]}

Cucchiara, Salvatore ^{[10
]}

Kim, Cecilia E. ^{[1
]}

Frackelton, Edward C. ^{[1
]}

Annaiah, Kiran ^{[1
]}

Glessner, Joseph T. ^{[1
]}

Santa, Erin ^{[1
]}

Willson, Tara ^{[11
]}

Eckert, Andrew W. ^{[1
]}

Bonkowski, Erin ^{[11
]}

Shaner, Julie L. ^{[1
]}

Smith, Ryan M. ^{[1
]}

Otieno, F. George ^{[1
]}

Peterson, Nicholas ^{[2
,3
]}

Abrams, Debra J. ^{[6
]}

Chiavacci, Rosetta M. ^{[1
]}

Grundmeier, Robert ^{[12
,13
]}

Mamula, Petar ^{[6
]}

Tomer, Gitit ^{[11
]}

Piccoli, David A. ^{[6
]}

Monos, Dimitri S. ^{[14
,15
]}

Annese, Vito ^{[16
,17
]}

Denson, Lee A. ^{[11
]}

Grant, Struan F. A. ^{[1
,12
,18
]}

Hakonarson, Hakon ^{[1
,12
,18
]}

机构：

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

[2] Med Coll Wisconsin, Milwaukee, WI 53226 USA

[3] Childrens Res Inst, Dept Pediat, Milwaukee, WI 53226 USA

[4] Childrens Hlth Care Atlanta, Atlanta, GA 30322 USA

[5] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA

[6] Childrens Hosp Philadelphia, Abramson Res Ctr, Dept Pediat, Philadelphia, PA 19104 USA

[7] Childrens Hosp Philadelphia, Abramson Res Ctr, Div Gastroenterol, Philadelphia, PA 19104 USA

[8] Primary Childrens Med Ctr, Salt Lake City, UT 84132 USA

[9] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT 84132 USA

[10] Univ Roma La Sapienza, Pediat Gastroenterol & Liver Unit, I-00185 Rome, Italy

[11] Childrens Hosp, Med Ctr, Div Gastroenterol, Cincinnati, OH 45229 USA

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

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

[14] Childrens Hosp Philadelphia, Div Immunol, Philadelphia, PA 19104 USA

[15] Childrens Hosp Philadelphia, Div Pathol, Philadelphia, PA 19104 USA

[16] Casa Sollievo Sofferenza Hosp, IRCCS, Unit Endoscopy, I-71013 San Giovanni Rotondo, Italy

[17] Casa Sollievo Sofferenza Hosp, IRCCS, Gastroenterol Unit, I-71013 San Giovanni Rotondo, Italy

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

来源：

NATURE GENETICS | 2008年 / 40卷 / 10期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ng.203

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 x 10(-8) and 6.95 x 10(-8), respectively; odds ratio (OR) 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 x 10(-8); OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.

引用

页码：1211 / 1215

页数：5

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