Elevated plasma triglycerides increase risk of psoriasis: A cohort and Mendelian randomization study.

BACKGROUND:It is increasingly clear that triglyceride-rich lipoproteins are proinflammatory and cause low-grade systemic inflammation. However, it is currently unknown whether elevated plasma triglycerides are causally related to development of psoriasis, a skin disorder driven by chronic inflammation. OBJECTIVE:To determine if elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis. METHODS:Consecutive individuals from the Copenhagen General Population Study (CGPS) were included. We used plasma triglycerides (n = 108,043) and a weighted triglyceride allele score (n = 92,579) on nine known triglyceride-altering genetic variants. Genetic results were replicated in 337,159 individuals from the UK biobank. Psoriasis was ICD10-code hospital contact in main analyses, and prescription of topical antipsoriatics for mild psoriasis in sensitivity analysis. RESULTS:During a median 9.3 years (0.1-15.1) of follow-up (from 2003-2015 through 2018), 855 (1%) individuals were diagnosed with psoriasis by ICD-10 in observational analysis and 772 (1%) in Mendelian randomization analysis. In observational analysis, multivariable adjusted hazard ratio for psoriasis by ICD-10 were 1.26 (95% CI:1.15-1.39) per doubling in plasma triglycerides with a corresponding causal, genetic risk ratio of 2.10 (1.30-3.38). Causality was confirmed in the UK biobank. Results were similar but slightly attenuated when we used topical antipsoriatics prescription for mild psoriasis. CONCLUSION:Elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis.