Original ResearchFull Report: Basic and Translational—Alimentary TractCharacterization of Genetic Loci That Affect Susceptibility to Inflammatory Bowel Diseases in African Americans
Section snippets
Study Population and Phenotyping
The study population included unrelated self-identified non-Hispanic AA volunteers recruited from 3 coordinating centers: (1) Johns Hopkins: Multicenter African American IBD Study (MAAIS) coordinated by Johns Hopkins IBD Genetics Research Center (GRC) of the National Institutes of Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium (IBDGC) with recruitment from 13 collaborating IBD centers and 4 other IBDGC GRCs,5 and additional AA control samples from the controls from
Results
After quality-control measures were performed, 3308 samples (1511 IBD cases and 1797 controls) and 130,241 unique autosomal SNPs remained for association and admixture analyses (Supplementary Figures 1 and 2). Mean YRI was higher in controls than in cases (81.7% ± 9.7% vs 80.0% ± 10.3%; P < 1 × 10-5), and also differed by coordinating centers (P < 1 × 10-10), with YRI proportion lowest for AAs from the American west coast, similar to other genetic studies24 (Supplementary Table 1).
Five
Discussion
In this study of IBD genetics in the AA population, we assembled the largest set of cases and controls (more than 4 times larger than any prior AA IBD study and the first genetic study of AA UC), evaluated for replication the of majority of established IBD associations, and we interrogated the majority of known IBD loci for novel associations. We also performed pathway and eQTL analyses to further inform about the nature of AA IBD genetics. Although our genotyping platform (not being GWA)
Acknowledgments
The authors are grateful to all of the patients and the controls that volunteered to join this study. This study is dedicated to Dr Linda Kao, who helped plan and direct the study, and passed away just before the study’s completion.
Ming-Hsi Wang's current affiliaton is, Department of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, Florida.
IBDGC sample recruitment was from the Meyerhoff Inflammatory Bowel Disease Center at The Johns Hopkins Hospital and Johns Hopkins
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2021, GastroenterologyCitation Excerpt :Although many of the variants associated with risk had also been identified in European populations, some were associated with IBD in patients of African descent only. For example, single-nucleotide polymorphisms in the signal transducer and activator of transcription 5A gene (STAT5A) and STAT53 genes were associated with CD.38 Single nucleotide polymorphisms in the zinc finger protein 649 gene (ZNF649) and limbic system–associated membrane protein gene (LSAMP) were associated with UC in AA persons.39
Candidate polymorphisms and susceptibility to inflammatory bowel disease: A systematic review and meta-analysis
2020, GeneCitation Excerpt :Through published GWAS meta-analysis, 231 independent SNPs within 200 loci are associated with the risk of IBD (Liu, 2015). Many genetic studies have resulted in the identification of several gene polymorphisms for IBD, including NOD2/CARD15 (Martinez-Chamorro, 2016); IL-10 (Wu, 2016); IL23R (Huang, 2015). The present meta-analyses of IBD focus on five immunomodulatory genes including IRF5, PTGER4, IL12B.
African Ancestry Proportion Influences Ileal Gene Expression in Inflammatory Bowel Disease
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Conflicts of interest The authors disclose no conflicts.
Funding This work supported by National Institutes of Health (NIH) grants DK062431 (S.R.B.), DK087694 (S.K.), DK062413 (D.P.B.M and K.T), DK046763-19, AI067068, and U54DE023789-01 (D.P.B.M.), DK062429 and DK062422 (J.H.C.), DK062420 (R.H.D.), DK062432 (J.D.R.), and DK062423 (M.S.S.). Additional support from Harvey M. and Lynn P. Meyerhoff Inflammatory Bowel Disease Center, the Morton Hyatt Family, the Buford and Linda Lewis family (S.R.B.); endowed professorship from Marcus foundation (S.K.); The Joshua L and Lisa Z Greer Endowed Chair, HS021747 from the Agency for Healthcare Research and Quality, grant 305479 from the European Union, and The Leona M. and Harry B. Helmsley Charitable Trust (D.P.B.M.); from the Veterans Administration HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413) and the Michael E. DeBakey VA Medical Center (J.K.H.). PARC control samples supported by NIH/National Heart, Lung, and Blood Institute grant HL06957 (Ronald M. Krauss, principal investigator). Rheumatoid arthritis control samples recruited and supported by the Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR), NIH grants N01-AR-02247 and AR-6-2278 (S.L.B.) and the University of Alabama General Clinical Research Center (M01-RR-00032); systemic lupus erythematosus control samples recruited and supported by the PROFILE Study group coordinated at the University of Alabama Birmingham and supported by NIH grants P01-AR49084 (R.P.K.) and M01-RR-00032; type 1 diabetes control samples recruited and supported by the Type 1 Diabetes Genetics Consortium U01 DK062418 (S.S.R.), and sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Center for Human Genome Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Juvenile Diabetes Research Foundation. C.L.S. is supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.
Author names in bold designate shared co-first authorship.
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Deceased.
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Authors share co-first authorship
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Authors share co-senior authorship.