Genetically predicted metabolites mediate the association between lipidome and malignant melanoma of skin

Abstract

ObjectiveTo investigate the causal relationship between lipidome and malignant melanoma of skin (MMOS), while identifying and quantifying the role of metabolites as potential mediators.MethodsA two-sample Mendelian randomization (MR) analysis of lipid species (n=7174) and MMOS was performed using pooled data from genome-wide association studies (GWAS). In addition, we quantified the proportion of metabolite-mediated lipidome effects on MMOS by two-step MR.ResultsThis study identified potential causal relationships between 11 lipids and MMOS, and 40 metabolites and MMOS, respectively. Phosphatidylethanolamine (18:0_18:2) levels mined from 179 lipids by MR Analysis increased the risk of MMOS (OR: 1.962; 95%CI:1.298,2.964; P=0.001). There is no strong evidence for a relationship between genetically predicted MMOS and phosphatidylethanolamine (18:0_18:2) levels (P=0.628). The proportion of gene predictions for phosphatidylethanolamine (18:0_18:2) levels mediated by 1-stearoyl-(glycosylphosphatidylinositol) GPI (18:0) levels was 12.40%.ConclusionThis study identifies 1-stearoyl-GPI (18:0) levels as a potential mediator that may mediate the causal relationship between phosphatidylethanolamine (18:0_18:2) levels and MMOS, This provides direction for the investigation of MMOS, but further research of other possible potential mediators is still needed.