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Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.
Laufer, Vincent A; Tiwari, Hemant K; Reynolds, Richard J; Danila, Maria I; Wang, Jelai; Edberg, Jeffrey C; Kimberly, Robert P; Kottyan, Leah C; Harley, John B; Mikuls, Ted R; Gregersen, Peter K; Absher, Devin M; Langefeld, Carl D; Arnett, Donna K; Bridges, S Louis.
Afiliación
  • 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.
  • Mikuls TR; United States Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
  • Gregersen PK; VA Nebraska-Western Iowa Health Care System and the Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
  • Absher DM; Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, USA.
  • Langefeld CD; Hudson Alpha Institute for Biotechnology, Huntsville, AL, USA.
  • Arnett DK; Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
  • Bridges SL; University of Kentucky College of Public Health, Lexington, KY, USA.
Hum Mol Genet ; 28(5): 858-874, 2019 03 01.
Article en En | MEDLINE | ID: mdl-30423114
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Negro o Afroamericano / Predisposición Genética a la Enfermedad Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Negro o Afroamericano / Predisposición Genética a la Enfermedad Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido