Fig. 3

An illustrative mechanistic diagram showing the protective effect of genetically predicted plasma caffeine levels on osteoarthritis liability^(a), mediated through body mass index^(b). The figure extends to a representation of our findings that genetically predicted caffeine levels drive consumption behaviour^(c), but not vice versa^(d). In keeping with our findings, prior studies have reported a positive association between caffeine consumption and body mass index and osteoarthritis risk^(e). Mendelian randomization estimates are scaled per one standard deviation increase in plasma caffeine levels and are shown with their corresponding 95% confidence intervals in parenthesis. Citations included [1] Cornelis et al. (2016); [2] Nicolopoulos et al. (2020); [3] Lee (2018); [4] Zhang et al. (2021). Abbreviations: AHR: aryl hydrocarbon receptor, BMI: body mass index, CYP1A2: cytochrome P450 isoform 1A2. This figure was created using Biorender.com