Although previous studies have indicated an association between low-density lipoprotein (LDL) and skin diseases, their causal effects remain inconclusive. This study aimed to assess the causal relationship between genetically proxied lipid-lowering drugs and skin cancers and psoriasis.
Two-sample Mendelian randomization (MR) analysis was performed using single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was used to determine causal relationships. The “leave-one-out” sensitivity test, Cochran’s Q-statistic and MR-Egger intercept were used to assess heterogeneity and horizontal pleiotropy.
We identified 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase subtilisin-kexin type 9 (PCSK9) as genetically proxied lipid-lowering drugs. Genetically proxied inhibition of HMGCR (stains) was causally associated with reduced risk of nonmelanoma skin cancer (OR 0.982, 95% CI 0.967–0.997,
This study revealed the existing HMGCR inhibitors (stains) might be protective for reducing nonmelanoma skin cancer risk, and HMGCR inhibitors (stains) and PCSK9 inhibitor (alirocumab) might be promising for reducing psoriasis risk in the European population.