Year: 2018
Type: article
Study design: Observational Study
Abstract: 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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddy395
Institutions: University of Alabama at Birmingham, Cincinnati Children's Hospital Medical Center, United States Department of Veterans Affairs, Veterans Health Administration, Cincinnati VA Medical Center, VA Nebraska Western Iowa Health Care System, University of Nebraska Medical Center, Northwell Health, Feinstein Institute for Medical Research, HudsonAlpha Institute for Biotechnology, Wake Forest University Health Sciences, Wake Forest University, University of Kentucky
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: NIAMS Multidisciplinary Clinical Research Center, G1313816191, Genetic Architecture of Rheumatoid Arthritis in African-Americans, Genome-Wide Association Study in African-Americans with Rheumatoid Arthritis, Center for Clinical and Translational Science, Better Outcomes for Children: Promoting Excellence in Healthcare Genomics to Inform Policy, G404386980, Discovering Novel Genetic and Environmental Risk Factors for RA in African Americ, G7069741293, UAB Center for Clinical and Translational Science (CCTS), G9000010268, G9000050404, G9000105038, G9000169229
OpenAlex ID: W2911999331