Large-scale meta-analysis on rheumatoid arthritis across East Asian and European populations

Objective: Nearly 110 susceptibility loci for rheumatoid arthritis (RA) with modest effect sizes have been identified by population-based genetic association studies, suggesting a large number of undiscovered variants behind a highly polygenic genetic architecture of RA. Here, we performed the largest-ever trans-ancestral meta-analysis with the aim to identify new RA loci and to better understand RA biology underlying genetic associations.

Methods: Genome-wide RA association summary statistics in three large case-control collections consisting of 311,292 individuals of Korean, Japanese, and European populations were used in an inverse-variance-weighted fixed-effects meta-analysis. Several computational analyses using public omics resources were conducted to prioritize causal variants and genes, RA variant-implicating features (tissues, pathways, and transcription factors), and potentially repurposable drugs for RA treatment.

Results: We identified 11 new RA susceptibility loci th...