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

Abstract

BackgroundMendelian randomization (MR) has increasingly been utilized as a tool for establishing causal relations between modifiable exposures and osteoarthritis (OA).ObjectiveThe goal of this review was to summarize available MR studies of OA that evaluate the causal role of modifiable risk factors on OA.MethodsThis review was performed following the PRISMA‐ScR (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses 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.ResultsOur 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 LDL‐cholesterol.ConclusionsThese results highlight the potential benefits of weight reduction and improvement of sleep quality to reduce risk of OA and call for a better understanding of the relation of coffee consumption of serum calcium to OA risk.This article is protected by copyright. All rights reserved.image

Comparative Study on the Association Between Types of Physical Activity, Physical Activity Levels, and the Incidence of Osteoarthritis in Adults：The NHANES 2007–2020

“…The following information was gathered using a household structured questionnaire: age (20-44, 45-64, ≥ 65 years), gender (male and female), race (Mexican American, Other Hispanic, Non-Hispanic white, Non-Hispanic black and Other race), level of education (less than high school, high school, more than high school), Examination data included BMI (kg/m2). Laboratory data covered blood urea nitrogen (BUN, mmol/L) 12 , total calcium (Ca, mmol/L) 13 , phosphorus (P, mmol/L) 14 , triglycerides (TG, mmol/L) 15 , uric acid (UA, µmol/L) 16 , and total cholesterol (TC, mmol/L) 17 . As a nal point, questionnaire data included information on smoking behavior (Yes/No) 18 , alcohol consumption (Yes/No) 19 , hypertension (Yes/No) 20 , and diabetes (Yes/No) 21 .…”

Omeprazole and risk of osteoarthritis: insights from a mendelian randomization study in the UK Biobank

“…Over the last decade, a plethora of MR studies have been undertaken to pinpoint causal factors linked to OA. For instance, MR investigations have offered backing for causal relationships between OA and elevated adiposity, coffee intake, bone mineral density, and sleep disruption, alongside diminished levels of serum calcium and low-density lipoprotein cholesterol [ 30 ]. These findings emphasize the potential advantages of decreasing weight and enhancing sleep quality to lower the risk of OA, while also highlighting the necessity for gaining a deeper understanding of the correlation between coffee intake and serum calcium concentrations regarding OA risk.…”

Causal association between dried fruit intake and risk of osteoarthritis: A Mendelian randomization study

“…[ 6 ] Recent MR studies support a causal relationship between OA and lifestyle-related obesity, coffee intake, Bdensity, sleep disturbance, decreased serum calcium and LDL cholesterol levels. [ 7 ] No studies have reported using MR methods to test the causal effect of dried fruit intake and OA risk. Therefore, this study used a two-sample MR analysis to investigate whether dried fruit intake is causally associated with the risk of developing OA.…”