ArticleOsteoarthritis and cartilage open2026
DNAJB12 mediates the causal effect of obesity on knee osteoarthritis: A mendelian randomization study.
Article in Osteoarthritis and cartilage open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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8 authors.
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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 Results: Obesity causally influenced 243 circulating proteins. Among these, DNAJB12 showed a significant causal effect on KOA risk [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.24-1.95] and mediated 20.55% (95% CI 5.92-35.18%) of the obesity-to-KOA effect. Replication analyses supported the obesity-DNAJB12 and DNAJB12-KOA associations. Colocalization provided high-confidence evidence for a shared genetic signal between DNAJB12 pQTLs and KOA in the larger KOA GWAS dataset (PP·H4 = 0.9490). Multivariable MR implicated fat mass, but not fat-free mass, as the main driver of mediator protein changes and KOA risk. Conclusions: Obesity causally increases KOA risk, partially acting through obesity-regulated circulating protein DNAJB12. These findings highlight adiposity-driven pathways and fat mass reduction as potential strategies to mitigate obesity-associated KOA.
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