Serum Lipids and Risk of Incident Psoriasis: A Prospective Cohort Study from the UK Biobank Study and Mendelian Randomization Analysis

The association between dyslipidemia and psoriasis has been studied widely. However, which individual indicators of serum lipids determine an increasing risk of incident psoriasis is still underappreciated in prospective cohorts. On the basis of UK Biobank, we investigate the causal relationship between four serum lipids and incident psoriasis by Cox proportional hazard model and Mendelian randomization analysis. After adjusting for covariates, high-density lipoprotein deficiency (<1.0 mmol/l for men, <1.3 mmol/l for women) and high triglyceride level (≥1.7 mmol/l) at baseline were associated with 16.6% and 10.6% increased risk of incident psoriasis, respectively. The effects were more pronounced in women, with 16.9 and 19.7% additional risk of psoriasis, respectively. The effects in the younger group (aged <60 years) and obese group in women were also more pronounced. No similar effect was observed in low-density lipoprotein and total cholesterol. Our subsequent Mendelian randomization analysis reinforced the main finding that high-density lipoprotein deficiency and high triglyceride cause incident psoriasis genetically. In conclusion, serum high-density lipoprotein/triglyceride levels predict psoriasis, particularly in women, indicating a distinct role of lipids engaging in the pathogenesis of psoriasis modified by sex. More metabolic-targeted, sex-specific management of psoriasis is suggested in the future. The association between dyslipidemia and psoriasis has been studied widely. However, which individual indicators of serum lipids determine an increasing risk of incident psoriasis is still underappreciated in prospective cohorts. On the basis of UK Biobank, we investigate the causal relationship between four serum lipids and incident psoriasis by Cox proportional hazard model and Mendelian randomization analysis. After adjusting for covariates, high-density lipoprotein deficiency (<1.0 mmol/l for men, <1.3 mmol/l for women) and high triglyceride level (≥1.7 mmol/l) at baseline were associated with 16.6% and 10.6% increased risk of incident psoriasis, respectively. The effects were more pronounced in women, with 16.9 and 19.7% additional risk of psoriasis, respectively. The effects in the younger group (aged <60 years) and obese group in women were also more pronounced. No similar effect was observed in low-density lipoprotein and total cholesterol. Our subsequent Mendelian randomization analysis reinforced the main finding that high-density lipoprotein deficiency and high triglyceride cause incident psoriasis genetically. In conclusion, serum high-density lipoprotein/triglyceride levels predict psoriasis, particularly in women, indicating a distinct role of lipids engaging in the pathogenesis of psoriasis modified by sex. More metabolic-targeted, sex-specific management of psoriasis is suggested in the future.