The Causal relationship of adipokines with rheumatoid arthritis among European populations: a two-sample Mendelian randomization study

Abstract

BackgroundAdipokines played an important role in the pathogenesis of rheumatoid arthritis (RA). However, observational studies have indicated an inconsistent association between adipokines (adiponectin, resistin and leptin) and RA. Therefore, we tried to explore the causal effects of genetically predicted adipokines on RA by two-sample Mendelian randomization (MR) study.MethodsSummary statistics of RA were obtained from a genome-wide association study (GWAS) of European descent, including 14,361 RA cases and 43,923 controls. Based on three additional GWAS, we selected genetic variants as instrumental variables (IVs) that were related to adiponectin, resistin and leptin. The two-sample MR study was conducted to estimate causality between adipokines and RA by the inverse-variance weighted (IVW) method and weighted-median method. In addition, we applied MR-Egger regression, MR-PRESSO and leave-one-out analysis to evaluate the potential pleiotropy effects.ResultsWe screened a total of 12 single nucleotide polymorphisms (SNPs) for adipokines (7 SNPs for adiponectin, 3 SNPs for resistin and 2 SNPs for leptin). We found that resistin was positively related to risk of RA (the IVW method: OR: 1.28, 95% CI: 1.07-1.53, P-value = 0.007; the weighted median: OR: 1.25, 95% CI: 1.02-1.54, P-value = 0.035). However, based on the IVW method and weighted median, there was little evidence to support the causal relationship between adiponectin, leptin and RA. MR-Egger regression, MR-PRESSO and leave-one-out analysis did not indicate horizontal pleiotropy.ConclusionsOur MR study indicates that genetically predicted resistin is causally associated with risk of RA. However, there was little evidence to support the causality of adiponectin and leptin on RA, tentatively.