No abstract

No abstract

Background: Accumulating evidence from observational studies suggested that circulating adiponectin levels are associated with the risk of rheumatoid arthritis (RA), but the causality remains unknown. We aimed to assess the causal relationship of adiponectin with RA risk.Methods: Based on summary statistics from large-scale genome-wide association studies (GWAS), we quantified the genetic correlation between adiponectin and RA. Then bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship. Twenty single-nucleotide polymorphisms (SNPs) associated with adiponectin were selected as instrumental variables from a recent GWAS (n = 67,739). We applied theses SNPs to a large-scale GWAS for RA (14,361 cases and 43,923 controls) with replication using RA data from the FinnGen consortium (6,236 cases and 147,221 controls) and the UK Biobank (5,201 cases and 457,732 controls). The inverse-variance weighted (IVW) and multiple pleiotropy-robust methods were used for two-sample MR analyses.Results: Our analyses showed no significant genetic correlation between circulating adiponectin levels and RA [rG = 0.127, 95% confidence interval (CI): –0.012 to 0.266, P = 0.074]. In MR analyses, genetically predicted adiponectin levels were not significantly associated with the RA risk (odds ratio: 0.98, 95% CI: 0.88–1.09, P = 0.669). In the reverse direction analysis, there is little evidence supporting an association of genetic susceptibility to RA with adiponectin (β: 0.007, 95% CI: –0.003 to 0.018, P = 0.177). Replication analyses and sensitivity analyses using different models yielded consistent results.Conclusions: Our findings provided no evidence to support the causal effect of adiponectin levels on RA risk and of RA on circulating adiponectin levels.

Background There is very little information about the association between physical activity (PA) and the risk of rheumatoid arthritis (RA). The purpose of this study is to understand the effect of PA on subsequent risk of developing RA. Methods A literature search was performed in PubMed and Web of Science up to 19 September 2020. Observational studies examining associations between PA and the RA development were identified. Categorical and dose–response meta-analyses were both performed. Then two-sample Mendelian randomization (MR) analysis was conducted to interrogate the causal relationship by utilizing genetic instruments identified from a genome-wide association study of self-reported and accelerometer-based PA traits. Results Four eligible studies were included in the meta-analyses, involving 4213 RA cases among 255 365 participants. The summary relative risk (RR) of RA risk was 0.79 [95% confidence interval (CI): 0.72, 0.87] for the highest vs the lowest PA, and 0.85 (95% CI: 0.79, 0.92) for PA vs inactivity/occasional PA. However, we found no convincing evidence supporting a causal role of genetically predicted accelerometer-measured PA [odds ratio (OR): 0.97; 95% CI: 0.88, 1.08 per 1-SD unit increment], genetically predicted moderate-to-vigorous PA (OR: 1.08; 95% CI: 0.49, 2.39 per 1-SD unit increment) or genetically predicted vigorous PA ≥3 days/week (OR: 2.63; 95% CI: 0.05, 130.96) with RA risk. Conclusions The meta-analyses of the observational studies indicated that higher PA levels correlate with reduced risk of RA. In contrast to meta-analyses, the MR analyses reported here suggested PA may not help to prevent RA.

No abstract