Minor Genetic Overlap Among Rheumatoid Arthritis, Myocardial Infarction, and Myocardial Infarction Risk Determinants

Objective: To investigate whether a shared genetic susceptibility exists between rheumatoid arthritis (RA) and myocardial infarction (MI) - including major MI risk factors - and to quantify the degree of any such overlap. Methods: Genome-wide association study (GWAS) data for RA was constructed from a sample of 26,637 Swedish RA cases and RA-free controls. For MI, GWAS data was obtained from a previously published meta-analysis. Genome-wide genetic correlation was estimated via LD score regression. LAVA was employed to estimate local genetic correlations in similar to 2500 non-overlapping loci, including the major histocompatibility complex (MHC). The RA-free controls were used for reference panel data. We also assessed stratified estimates of both genome-wide and local genetic correlation, based on subsamples of seropositive and seronegative RA. Furthermore, genome-wide genetic correlation was estimated between RA and selected cardiovascular risk factors, to elucidate pleiotropic relationships. Results: Following quality control, our RA GWAS consisted of 25,826 individuals. Genome-wide genetic correlation between RA and MI was estimated to r(g)=0.13 (95%CI -0.03-0.29). Six regions exhibited significant local r(g) though none harbored any known risk SNPs for either of the two traits. Estimates were similar in both seropositive and seronegative RA. No statistically significant r(g) were observed between RA and any of the MI risk factors. Conclusions: Our findings indicate that genetic overlap between RA and MI is minor. Furthermore, genetic overlap between RA and MI risk factors seem unlikely to provide a major contribution to the increased risk of MI observed in RA.