Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease

Steven R Brant; David T Okou; Claire L Simpson; David J Cutler; Talin Haritunians; Jonathan P Bradfield; Pankaj Chopra; Jarod Prince; Ferdouse Begum; Archana Kumar; Chengrui Huang; Suresh Venkateswaran; Lisa W Datta; Zhi Wei; Kelly Thomas; Lisa J Herrinton; Jan-Micheal A Klapproth; Antonio J Quiros; Jenifer Seminerio; Zhenqiu Liu; Jonathan S Alexander; Robert N Baldassano; Sharon Dudley-Brown; Raymond K Cross; Themistocles Dassopoulos; Lee A Denson; Tanvi A Dhere; Gerald W Dryden; John S Hanson; Jason K Hou; Sunny Z Hussain; Jeffrey S Hyams; Kim L Isaacs; Howard Kader; Michael D Kappelman; Jeffry Katz; Richard Kellermayer; Barbara S Kirschner; John F Kuemmerle; John H Kwon; Mark Lazarev; Ellen Li; David Mack; Peter Mannon; Dedrick E Moulton; Rodney D Newberry; Bankole O Osuntokun; Ashish S Patel; Shehzad A Saeed; Stephan R Targan; John F Valentine; Ming-Hsi Wang; Martin Zonca; John D Rioux; Richard H Duerr; Mark S Silverberg; Judy H Cho; Hakon Hakonarson; Michael E Zwick; Dermot P.B McGovern; Subra Kugathasan

doi:10.1053/j.gastro.2016.09.032

Back

Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease

Journal article

Open access

Peer reviewed

Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease

Steven R Brant, David T Okou, Claire L Simpson, David J Cutler, Talin Haritunians, Jonathan P Bradfield, Pankaj Chopra, Jarod Prince, Ferdouse Begum, Archana Kumar, …

Gastroenterology (New York, N.Y. 1943), Vol.152(1), pp.206-217.e2

01/2017

DOI: https://doi.org/10.1053/j.gastro.2016.09.032

PMCID: PMC5164948

PMID: 27693347

Abstract

Genetic Analysis

Risk Factor

SNP

Trans-Ethnic

The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10−8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10−6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry.

Files and links (1)

url

https://doi.org/10.1053/j.gastro.2016.09.032View

Version of Record (VoR) Open

Metrics

27 Record Views

101 Times Cited - Web of Science

See more details

Details

Title: Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease
Creators: Steven R Brant - Department of Medicine, Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
David T Okou - Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
Claire L Simpson - Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee
David J Cutler - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia
Talin Haritunians - F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
Jonathan P Bradfield - Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Pankaj Chopra - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia
Jarod Prince - Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
Ferdouse Begum - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
Archana Kumar - Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
Chengrui Huang - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
Suresh Venkateswaran - Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
Lisa W Datta - Department of Medicine, Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Zhi Wei - Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Kelly Thomas - Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Lisa J Herrinton - Kaiser Permanente, Oakland, California
Jan-Micheal A Klapproth - University of Pennsylvania, Philadelphia, Pennsylvania
Antonio J Quiros - Department of Pediatrics, Medical University of South Carolina, Pediatric Center for Inflammatory Bowel Disorders, Summerville, South Carolina
Jenifer Seminerio - Department of Gastroenterology, Medical University of South Carolina Digestive Disease Center, Charleston, South Carolina
Zhenqiu Liu - F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
Jonathan S Alexander - Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana
Robert N Baldassano - Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Sharon Dudley-Brown - Department of Medicine, Johns Hopkins University Schools of Medicine & Nursing, Baltimore, Maryland
Raymond K Cross - Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
Themistocles Dassopoulos - Department of Medicine, Washington University School of Medicine, St Louis, Missouri
Lee A Denson - Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
Tanvi A Dhere - Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
Gerald W Dryden - Department of Medicine, University of Louisville, Louisville, Kentucky
John S Hanson - Charlotte Gastroenterology and Hepatology, Charlotte, North Carolina
Jason K Hou - Department of Medicine, Baylor College of Medicine; Veterans Affairs Health Services Research and Development Service, Center for Innovations in Quality Effectiveness and Safety; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
Sunny Z Hussain - Department of Pediatrics, Willis-Knighton Physician Network, Shreveport, Louisiana
Jeffrey S Hyams - Connecticut Children’s Medical Center, Hartford, Connecticut
Kim L Isaacs - Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Howard Kader - Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland
Michael D Kappelman - Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Jeffry Katz - Case Western Reserve University, Cleveland, Ohio
Richard Kellermayer - Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
Barbara S Kirschner - Department of Pediatrics, University of Chicago Comer Children's Hospital, Chicago, Illinois
John F Kuemmerle - Medicine and Physiology and Biophysics, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Virginia
John H Kwon - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
Mark Lazarev - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
Ellen Li - Department of Medicine, Stony Brook University School of Medicine, Stony Brook, New York
David Mack - Department of Pediatrics, University of Ottawa and Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
Peter Mannon - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
Dedrick E Moulton - Vanderbilt Children's Hospital, Nashville, Tennessee
Rodney D Newberry - Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri
Bankole O Osuntokun - Department of Pediatrics, Cook Children's Medical Center, Fort Worth, Texas
Ashish S Patel - Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
Shehzad A Saeed - Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
Stephan R Targan - F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
John F Valentine - University of Utah, Health Sciences, Salt Lake City, Utah
Ming-Hsi Wang - Division of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, Florida
Martin Zonca - Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan
John D Rioux - Department of Medicine, Université de Montréal and the Montreal Heart Institute Research Center, Montreal, Quebec, Canada
Richard H Duerr - Department of Medicine and Clinical and Translational Science Institute, School of Medicine and Department of Human Genetics, Graduate School of Public Health; University of Pittsburgh, Pittsburgh, Pennsylvania
Mark S Silverberg - Department of Medicine, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Toronto, Ontario, Canada
Judy H Cho - Medicine and Genetics, Icahn School of Medicine at Mount Sinai, Charles Bronfman Institute for Personalized Medicine, New York, New York
Hakon Hakonarson - Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Michael E Zwick - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia
Dermot P.B McGovern - F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
Subra Kugathasan - Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
Publication Details: Gastroenterology (New York, N.Y. 1943), Vol.152(1), pp.206-217.e2
Date published: 01/2017
Publisher: Elsevier Inc
Grant note: Harvey M. and Lynn P. Meyerhoff Inflammatory Bowel Disease Center Buford and Linda Lewis family DK062431; DK087694; DK062413; DK046763-19; AI067068; U54DE023789-01; DK062429; DK062422; DK062420; DK062432; DK062423 / The National Institutes of Health 305479 / Joshua L and Lisa Z Greer Endowed Chair Morton Hyatt Family
Academic Unit: Office of Research and Sponsored Programs; Medicine - Gastroenterology and Hepatology (RWJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031665520604646