Genetic association of lipids and lipid-lowering drug target genes with sarcoidosis

Objective: Todetermine the potential causal association between serum lipid levels and sarcoidosis, and to investigate the potential impact of lipid-lowering agents on sarcoidosis. Methods: Two-sample Mendelian randomization (TSMR) was used to investigate the association between lipid levels (including LDL-c, HDL-c, TG, and TC) and sarcoidosis risk. In addition, we conducted a comprehensive analysis of the relationship between lipid-lowering drugs and sarcoidosis, utilizing Mendelian randomization of drug targets (DMR). Results: According to the TSMR analysis, a positive correlation was observed between the serum LDL-c concentration and sarcoidosis incidence (n = 153 SNPs, OR = 1.232, 95% CI = 0.990 - 1.732; p = 0.031). Similarly, serum TG concentration was found to be positively associated with sarcoidosis (n = 52 SNPs, OR = 1.287, 95% CI = 1.024 - 1.617; p = 0.03). The DMR results demonstrated a positive correlation between PCSK9-mediated serum LDL-c levels and sarcoidosis (n = 35 SNPs, OR = 1.681, 95% CI = 1.220 - 2.315; p = 0.001). Similarly, serum TG levels mediated by LPL were positively associated with sarcoidosis (n = 28 SNPs, OR = 1.569, 95% CI = 1.223 - 2.012; p = 3.93E-04). Conclusions: This study suggested that elevated serum TG and LDL-c levels may increase the risk of sarcoidosis. The use of PCSK9 inhibitors and LPL-type lipid-lowering drugs is expected to increase the risk of sarcoidosis.