Osteoarthritis and cartilage open
DNAJB12 mediates the causal effect of obesity on knee osteoarthritis: A mendelian randomization study
By Wang A, Shan H, Cao X and 5 others.
Abstract
Objective
Obesity is a major risk factor for knee osteoarthritis (KOA), but the circulating proteins that mediate this association remain unclear. We aimed to identify obesity-regulated circulating proteins that causally influence KOA risk.
Design
We conducted a Mendelian Randomization based proteome-wide association study (MR-PWAS) analysis to investigate circulating proteins mediating the effect of obesity on KOA. Using a two-step Mendelian randomization-based proteome-wide association design, we first tested genetically predicted obesity against 4907 circulating proteins from deCODE. Obesity-associated proteins were then instrumented using cis-pQTLs and tested for causal effects on KOA. Candidate mediators were evaluated using product-of-coefficients mediation analysis, replication datasets, tissue-specific eQTL analysis, Bayesian colocalization and multivariable MR analysis.
