Common variants at five new loci associated with early-onset inflammatory bowel disease
Hakon Hakonarson and colleagues report the discovery of five new regions associated with susceptibility to early-onset inflammatory bowel disease. They also identify multiple loci previously implicated in the etiology of adult-onset Crohn's disease and/or ulcerative colitis as risk factors for...
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| Published in | Nature genetics Vol. 41; no. 12; pp. 1335 - 1340 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article Web Resource |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.12.2009
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1061-4036 1546-1718 1546-1718 |
| DOI | 10.1038/ng.489 |
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| Abstract | Hakon Hakonarson and colleagues report the discovery of five new regions associated with susceptibility to early-onset inflammatory bowel disease. They also identify multiple loci previously implicated in the etiology of adult-onset Crohn's disease and/or ulcerative colitis as risk factors for early-onset forms of these diseases.
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 IBD
1
. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene
IL27
(rs8049439,
P
= 2.41 × 10
−9
), 22q12 (rs2412973,
P
= 1.55 × 10
−9
), 10q22 (rs1250550,
P
= 5.63 × 10
−9
), 2q37 (rs4676410,
P
= 3.64 × 10
−8
) and 19q13.11 (rs10500264,
P
= 4.26 × 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. |
|---|---|
| AbstractList | Hakon Hakonarson and colleagues report the discovery of five new regions associated with susceptibility to early-onset inflammatory bowel disease. They also identify multiple loci previously implicated in the etiology of adult-onset Crohn's disease and/or ulcerative colitis as risk factors for early-onset forms of these diseases.
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 IBD
1
. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene
IL27
(rs8049439,
P
= 2.41 × 10
−9
), 22q12 (rs2412973,
P
= 1.55 × 10
−9
), 10q22 (rs1250550,
P
= 5.63 × 10
−9
), 2q37 (rs4676410,
P
= 3.64 × 10
−8
) and 19q13.11 (rs10500264,
P
= 4.26 × 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. 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 IBD. 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. 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 IBD 1 . We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 × 10 −9 ), 22q12 (rs2412973, P = 1.55 × 10 −9 ), 10q22 (rs1250550, P = 5.63 × 10 −9 ), 2q37 (rs4676410, P = 3.64 × 10 −8 ) and 19q13.11 (rs10500264, P = 4.26 × 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. 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 IBD (1). 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.sup.-9]), 22q12 (rs2412973, P = 1.55 x [10.sup.-9]), 10q22 I (rs1250550, P = 5.63 x [10.sup.-9] ), 2q37 (rs4676410, P= 3.64 x [10.sup.-8]) and 19q13.11 (rs10500264, P- 4.26 x [10.sup.-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. 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 IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 × 10^sup -9^), 22q12 (rs2412973, P = 1.55 × 10^sup -9^), 10q22 (rs1250550, P = 5.63 × 10^sup -9^), 2q37 (rs4676410, P = 3.64 × 10^sup -8^) and 19q13.11 (rs10500264, P = 4.26 × 10^sup -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. [PUBLICATION ABSTRACT] 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 IBD. 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.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 IBD. 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. |
| Audience | Academic |
| Author | Guthery, Stephen L Lee, Jessica Cucchiara, Salvatore Heyman, Melvin B Grant, Struan F A Imielinski, Marcin Taylor, Kent Bradfield, Jonathan P Glessner, Joseph T Flory, James H Kirschner, Barbara Zhang, Haitao Satsangi, Jack Saeed, Shehzad Russell, Richard K Ferry, George D Stephens, Michael Baldassano, Robert N Chiavacci, Rosetta M Walters, Thomas D Dubinsky, Marla Wang, Kai Dallapiccola, Bruno Van Limbergen, Johan Monos, Dimitri S Kim, Cecilia E Kugathasan, Subra McGovern, Dermot Hakonarson, Hakon Levine, Arie Grundmeier, Robert Abrams, Debra J Hou, Cuiping Silverberg, Mark S Sleiman, Patrick Otieno, George Castro, Massimo Denson, Lee Muise, Aleixo Frackelton, Edward C Griffiths, Anne Grand, Richard Wilson, David C Stempak, Joanne Piccoli, David Annese, Vito Essers, Jonah Daly, Mark Latiano, Anna |
| AuthorAffiliation | 1 Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA 12 Mendel Institute, La Sapienza University of Rome, IRCCS-CSS Hospital, S. Giovanni Rotondo, Italy 27 Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA 3 Division of Gastroenterology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA 5 Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Glasgow, UK 10 Center for Biomedical Informatics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA 24 The Center for Inflammatory Bowel Disease, Division of Gastroenterology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA 8 Department of Pediatrics, Emory University School of Medicine and Children’s Health Care of Atlanta, Atlanta, Georgia, USA 16 University of Chicago Comer Children’s Hospital, Chicago, Illinois, USA 19 Pediatric Gastroenterology Unit, Wolfson Medical Cent |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19915574$$D View this record in MEDLINE/PubMed |
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| Copyright | Springer Nature America, Inc. 2009 COPYRIGHT 2009 Nature Publishing Group Copyright Nature Publishing Group Dec 2009 2009 Nature America, Inc. All rights reserved. 2009 |
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| DOI | 10.1038/ng.489 |
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| References | Rioux (CR10) 2007; 39 Duerr (CR22) 2006; 314 Cho (CR3) 2008; 8 Van Limbergen, Wilson, Satsangi (CR2) 2009; 10 Luca (CR20) 2008; 82 Parkes (CR23) 2007; 39 Franke (CR6) 2008; 40 Kugathasan (CR1) 2008; 40 Steinman (CR16) 2007; 13 Hakonarson (CR18) 2007; 448 Purcell (CR24) 2007; 81 Dixon (CR14) 2007; 39 Vernier-Massouille (CR8) 2008; 135 Silverberg (CR7) 2009; 41 CR11 Fisher (CR4) 2008; 40 Barrett (CR5) 2008; 40 Van Limbergen (CR9) 2008; 135 Libioulle (CR12) 2007; 3 Bettelli, Oukka, Kuchroo (CR17) 2007; 8 Barrett (CR13) 2009; 41 Li, Thyssen, Beliakoff, Sun (CR15) 2006; 281 Patterson, Price, Reich (CR21) 2006; 2 Pritchard, Stephens, Donnelly (CR19) 2000; 155 N Patterson (BFng489_CR21) 2006; 2 AL Dixon (BFng489_CR14) 2007; 39 A Franke (BFng489_CR6) 2008; 40 J Van Limbergen (BFng489_CR9) 2008; 135 S Kugathasan (BFng489_CR1) 2008; 40 JD Rioux (BFng489_CR10) 2007; 39 JC Barrett (BFng489_CR13) 2009; 41 D Luca (BFng489_CR20) 2008; 82 SA Fisher (BFng489_CR4) 2008; 40 JK Pritchard (BFng489_CR19) 2000; 155 C Libioulle (BFng489_CR12) 2007; 3 J Van Limbergen (BFng489_CR2) 2009; 10 L Steinman (BFng489_CR16) 2007; 13 G Vernier-Massouille (BFng489_CR8) 2008; 135 X Li (BFng489_CR15) 2006; 281 BFng489_CR11 H Hakonarson (BFng489_CR18) 2007; 448 JH Cho (BFng489_CR3) 2008; 8 JC Barrett (BFng489_CR5) 2008; 40 E Bettelli (BFng489_CR17) 2007; 8 S Purcell (BFng489_CR24) 2007; 81 MS Silverberg (BFng489_CR7) 2009; 41 RH Duerr (BFng489_CR22) 2006; 314 M Parkes (BFng489_CR23) 2007; 39 |
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| Snippet | Hakon Hakonarson and colleagues report the discovery of five new regions associated with susceptibility to early-onset inflammatory bowel disease. They also... 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.... 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.... |
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| SubjectTerms | Age of Onset Agriculture Animal Genetics and Genomics Biomedical and Life Sciences Biomedicine Bowel disease Cancer Research Chromosome Mapping Colitis, Ulcerative - genetics Gastroenterology & hepatology Gastroentérologie & hépatologie Gene Function Genetic aspects Genetic Variation Genome, Human Genome-Wide Association Study Hospitals Human Genetics Human health sciences Humans Inflammatory bowel disease Inflammatory bowel diseases Inflammatory Bowel Diseases - epidemiology Inflammatory Bowel Diseases - genetics letter Medical research Meta-analysis Nutrition research Quantitative trait loci Risk factors Sciences de la santé humaine Studies Young adults |
| Title | Common variants at five new loci associated with early-onset inflammatory bowel disease |
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