دورية أكاديمية
أعرض في EDS

Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.

التفاصيل البيبلوغرافية
العنوان: Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.
المؤلفون: Laufer VA; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Tiwari HK; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA., Reynolds RJ; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Danila MI; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Wang J; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA., Edberg JC; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Kimberly RP; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Kottyan LC; Center for Autoimmune Genetics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Harley JB; Center for Autoimmune Genetics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; United States Department of Veterans Affairs Medical Center, Cincinnati, OH, USA., Mikuls TR; VA Nebraska-Western Iowa Health Care System and the Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA., Gregersen PK; Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, USA., Absher DM; Hudson Alpha Institute for Biotechnology, Huntsville, AL, USA., Langefeld CD; Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA., Arnett DK; University of Kentucky College of Public Health, Lexington, KY, USA., Bridges SL Jr; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
المصدر: Human molecular genetics [Hum Mol Genet] 2019 Mar 01; Vol. 28 (5), pp. 858-874.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: IRL Press at Oxford University Press Country of Publication: England NLM ID: 9208958 Publication Model: Print Cited Medium: Internet ISSN: 1460-2083 (Electronic) Linking ISSN: 09646906 NLM ISO Abbreviation: Hum Mol Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford, England ; New York : IRL Press at Oxford University Press, c1992-
مواضيع طبية MeSH: Genetic Predisposition to Disease*, Black or African American/*genetics , Arthritis, Rheumatoid/*epidemiology , Arthritis, Rheumatoid/*genetics, Aged ; Ethnicity/genetics ; Female ; Genetic Linkage ; Genetic Loci ; Genome-Wide Association Study ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide
مستخلص: Large meta-analyses of rheumatoid arthritis (RA) susceptibility in European (EUR) and East Asian (EAS) populations have identified >100 RA risk loci, but genome-wide studies of RA in African-Americans (AAs) are absent. To address this disparity, we performed an analysis of 916 AA RA patients and 1392 controls and aggregated our data with genotyping data from >100 000 EUR and Asian RA patients and controls. We identified two novel risk loci that appear to be specific to AAs: GPC5 and RBFOX1 (PAA < 5 × 10-9). Most RA risk loci are shared across different ethnicities, but among discordant loci, we observed strong enrichment of variants having large effect sizes. We found strong evidence of effect concordance for only 3 of the 21 largest effect index variants in EURs. We used the trans-ethnic fine-mapping algorithm PAINTOR3 to prioritize risk variants in >90 RA risk loci. Addition of AA data to those of EUR and EAS descent enabled identification of seven novel high-confidence candidate pathogenic variants (defined by posterior probability > 0.8). In summary, our trans-ethnic analyses are the first to include AAs, identified several new RA risk loci and point to candidate pathogenic variants that may underlie this common autoimmune disease. These findings may lead to better ways to diagnose or stratify treatment approaches in RA.
(© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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معلومات مُعتمدة: T32 AR069516 United States AR NIAMS NIH HHS; R37 AI024717 United States AI NIAID NIH HHS; U01 HG008666 United States HG NHGRI NIH HHS; K01 AR060848 United States AR NIAMS NIH HHS; UL1 TR001417 United States TR NCATS NIH HHS; P01 AR049084 United States AR NIAMS NIH HHS; P60 AR048095 United States AR NIAMS NIH HHS; UL1 TR003096 United States TR NCATS NIH HHS; R01 AR057202 United States AR NIAMS NIH HHS; K23 AR062100 United States AR NIAMS NIH HHS
تواريخ الأحداث: Date Created: 20181114 Date Completed: 20200311 Latest Revision: 20221207
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6381313
DOI: 10.1093/hmg/ddy395
PMID: 30423114
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2083
DOI:10.1093/hmg/ddy395