Background: Rheumatoid arthritis (RA) is one of the chronic inflammatory diseases that primarily influences the joints, and its prevalence is 0.5-1.0%. Previous studies have shown that there are differences in the genetic structure of RA between European and Asian populations, and most of the studies have been conducted using meta-analysis. This study analyzed the genetic structure of rheumatoid arthritis in European and Asian populations using a new method.
Methods: The Genome-Wide Association Study (GWAS) summary statistics of RA from Europe (N=8383) and Asia (N=19190) were derived from an article published in Nature. First, the GWAS data was divided into 1368 blocks, in which SNPs were approximately independent of linkage disequilibrium (LD). Second, we calculated the LD matrix of SNP in each block by using PLINK 1.9. Then, PESCA analysis was performed to detect population-specific/shared risk genes of RA. Finally, Metascape platform was used to perform gene set enrichment analysis.
Results: In European population, we found multiple genes which were associated with RA, including HLA-DPA1, HLA-DPB1 (rs2856822, PTP=1.000), MICA (rs2844518, PTP=1.000). In Asian population, C6orf10 (rs3129915, PTP=1.000), PTPN2 (rs2847288, PTP=0.995), were significant related to RA. The population-shared genes included PADI2 (rs2235920, PTP=1.000), STAT4 (rs12612769, PTP=1.000). Furthermore, gene sets enrichment analysis reported population-specific/shared pathway terms, such as interferon-gamma-mediated signaling pathway (P=2.884×10-9), negative regulation of innate immune response (P=1.841×10-7), protein-arginine deiminase activity (P=7.047×10-8).
Conclusions: The results of our study indicate differences in risk loci between Asian and European populations, which provided clues for exploring the population-specific/shared genetics and pathogenesis of RA.