Adiponectin and Risk of Psoriasis: Observational and Mendelian Randomization Studies in up to 900 000 Individuals

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder often associated with obesity. Adiponectin, an anti-inflammatory protein-hormone secreted by adipose tissue, may be a link between obesity and psoriasis. We hypothesized that low plasma adiponectin is associated with an increased risk of psoriasis in observational and causal genetic studies. METHODS: In observational analyses, we used information on plasma adiponectin and psoriasis in 30 045 individuals from the Copenhagen General Population Study (CGPS). In one-sample Mendelian randomization analyses, we used genetic information on adiponectin and psoriasis in 107 308 individuals from the CGPS. In two-sample Mendelian randomization analyses, we used genetic information on adiponectin from the ADIPOGen consortium and genetic information on psoriasis in 373 338 and 462 933 individuals from the FinnGen study and UK Biobank (UKB). RESULTS: In observational analyses, a 1-unit log-transformed higher plasma adiponectin was associated with a hazard ratio (HR) for psoriasis of 0.67 (95% confidence interval: 0.48-0.94) in an age- and sex-adjusted model but not in a multivariable adjusted model including obesity measures with a HR of 0.95 (0.66-1.35). In genetic one-sample Mendelian randomization analysis, a 1-unit log-transformed higher plasma adiponectin was not associated with a causal risk ratio for psoriasis of 1.33 (0.77-2.32) in the CGPS. In two-sample Mendelian randomization analyses, a 1-unit log-transformed higher plasma adiponectin was not associated with causal risk ratios for psoriasis of 0.96 (0.81-1.14) in FinnGen and 1.00 (1.00-1.01) in UKB. CONCLUSIONS: Low plasma adiponectin is associated with increased risk of psoriasis in age- and sex-adjusted observational analyses; however, this was not the case after adjustment for obesity measures or in causal genetic analyses.