Osteoarthritis & stroke: a bidirectional mendelian randomization study

Abstract

Objective: The epidemiological evidence on the link between osteoarthritis (OA) and stroke remains inconclusive. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) study to determine the causality relationship between OA and stroke.

Design: Summary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. The data for OA at any site (n = 455,211), knee OA (n = 403,124), and hip OA (n = 393,873) were obtained from a meta-analysis of GWAS available in the UK Biobank and Arthritis Research UK Osteoarthritis Genetics resources. The MEGASTROKE consortium provided data for stroke (n = 446,696), ischemic stroke (IS) (n = 440,328) and its subtypes, and intracerebral hemorrhage (ICH) (n = 3,026). The main MR analysis was conducted by the inverse variance weighted (IVW) method. MR-Egger regression, MR pleiotropy residual sum and outlier, weighted median, Cochran Q statistic, and leave-one-out analysis approach were leveraged as supplements.

Results: We detected that higher risk of hip OA was significantly associated with overall stroke [IVW odds ratio (OR): 1.12, 95% confidence interval (CI): 1.06-1.20, P = 0.0002], IS (OR: 1.13, 95%CI: 1.06-1.21, P = 0.0003), and small vessel IS (OR: 1.25, 95%CI: 1.10-1.42, P = 0.0006). However, we found no evidence that stroke and subtypes had casual effects on OA in the reverse MR analyses.

Conclusions: The present study provides genetic support that hip OA is a potential risk factor for overall stroke, IS, and small vessel IS. Further studies are warranted to elucidate the underlying mechanisms of causal associations between site-specific OA and stroke subtypes.

Keywords: Bidirectional; Mendelian randomization; Osteoarthritis; Stroke.