Causal association between body mass index and risk of rheumatoid arthritis: A Mendelian randomization study.

Abstract

This study aimed to examine whether body mass index (BMI) is causally associated with rheumatoid arthritis (RA). A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median and MR-Egger regression methods was performed. We used the publicly available summary statistics data sets of genome-wide association studies (GWAS) meta-analyses for BMI in individuals of European descent (n=322154; GIANT consortium) as the exposure and a GWAS for noncancer illness code self-reported: RA from the individuals included in the UK Biobank (total n=337159; case=7480, control=329679) as the outcome. We selected 68 single nucleotide polymorphisms at genome-wide significance from GWASs on BMI as the instrumental variables. The IVW method showed evidence to support a causal association between BMI and RA (beta=0.003, SE=0.001, P=0.033). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept=-3.54E-05; P=0.736), but it showed no causal association between BMI and RA (beta=0.004, SE=0.004, P=0.302). However, the weighted median approach yielded evidence of a causal association between BMI and RA (beta=0.006, SE=0.002, P=0.004). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy. The results of MR analysis support that BMI may be causally associated with an increased risk of RA.