Rheumatoid arthritis and coronary atherosclerosis: a two-sample Mendelian randomization study.

OBJECTIVES

The relationship between rheumatoid arthritis (RA) and coronary atherosclerosis is widely concerned, but observational studies have not clarified causality. We performed two-sample Mendelian randomization (MR) study to assess the causal association between RA and coronary atherosclerosis.

METHODS

we mainly conducted MR analysis using the inverse variance weighted (IVW) approach. Weighted median, MR-Egger regression and maximum likelihood were conducted as sensitivity analyses for supplementary analysis. Multivariate MR also were performed to validate the results of two-sample MR. Furthermore, we performed the MR-Egger intercept, MR-PRESSO, Cochran's Q test, and "Leave-one-out" to assess the levels of pleiotropy and heterogeneity.

RESULTS

IVW result showed a positive link between genetic predisposition to RA and increased relative risk of coronary atherosclerosis (OR: 1.0021, 95%CI 1.0011-1.0031, P < 0.05). The result was confirmed by the weighted median method (OR: 1.0028, 95%CI 1.0014-1.0042, P < 0.05), MR-Egger regression (OR: 1.0031, 95%CI 1.0012-1.0049, P < 0.05) and maximum likelihood (OR: 1.0021, 95%CI 1.0011-1.0030, P < 0.05). Multivariate MR also reached a consistent conclusion. In addition, MR-Egger intercept (P = 0.20) and MR-PRESSO (P = 0.06) did not provide evidence of horizontal pleiotropy. Meanwhile, the results of Cochran's Q test (P = 0.05) and "Leave-one-out" failed to detect significant heterogeneity.

CONCLUSION

The result of the two-sample MR analysis found genetic evidence to support the positive causal association between RA and coronary atherosclerosis, suggesting that active intervention for RA may reduce the incidence of coronary atherosclerosis.