Causal Factors for Osteoarthritis: A Scoping Review of Mendelian Randomization Studies

Mendelian randomization (MR) has increasingly been utilized as a tool for establishing causal relations between modifiable exposures and osteoarthritis (OA). The goal of this review was to summarize available MR studies of OA that evaluate the causal role of modifiable risk factors on OA.

This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews model. We performed a literature search for relevant studies published before December 2021 across multiple databases using the search terms "osteoarthritis" and ("Mendelian randomization" or "polygenic risk score"). We reported the MR estimates of causal associations between exposures and OA and then assessed methodologic quality of abstracted studies according to their efforts to validate the three key MR assumptions.

Our search identified 45 studies reporting on 141 exposure-association analyses. All studies performed a formal instrumental variable analysis to estimate the causal effect of exposure on OA. Causal associations (P < 0.05) were reported in 60 of these analyses representing 36 unique publications, and MR-Egger sensitivity analyses were performed in 45 of these analyses. MR studies provided support for causal associations of OA with increased levels of adiposity, coffee consumption, bone mineral density, and sleep disturbance, and decreased levels of serum calcium and low-density lipoprotein cholesterol.

These results highlight the potential benefits of weight reduction and improvement of sleep quality to reduce the risk of OA and call for a better understanding of the relations of coffee consumption and serum calcium to OA risk.