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Susceptibility to RA in African Americans Examined

Hum Mol Genet; ePub 2018 Nov 13; Laufer, et al

Large meta-analyses of rheumatoid arthritis (RA) susceptibility in European and East Asian populations have identified >100 RA risk loci, but genome-wide studies of RA in African-Americans are absent. In order to address this disparity, researchers performed an analysis of 916 African-American patients with RA and 1,392 controls, and aggregated their data with genotyping data from >100,000 European and Asian patients with RA and controls. Findings include:

  • 2 novel risk loci that appear to be specific to African-Americans were identified: GPC5 and RBFOX1 (pAA < 5 x 10-9).
  • Most RA risk loci are shared across different ethnicities, but among discordant loci, strong enrichment of variants having large effect sizes was observed.
  • There was strong evidence of effect concordance for only 3 of the 21 largest effect index variants in Europeans.
  • Addition of African-American data to those of European and East Asian descent enabled identification of 7 novel high confidence candidate pathogenic variants.

Laufer VA, Tiwari HK, Reynolds RJ, et al. Genetic influences on susceptibility to rheumatoid arthritis in African-Americans. [Published online ahead of print November 13, 2018]. Hum Mol Genet. doi:10.1093/hmg/ddy395.

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