A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context

Researchers performed a GWAS on serum metabolites in the Finnish Metabolic Syndrome In Men (METSIM) cohort (n=6263) and leveraged the high correlation structure between metabolites to increase the power of association tests via the Covariates for Multi-phenotype Studies (CMS) method.

The study identified 588 significant SNP-metabolite associations to 158 serum metabolites, of which 228 were new associations. The results highlighted genes with strong pleiotropic effects and found that 13 master metabolic regulator genes (LIPC, CETP, PCSK9 and LDLR among others) capture over 75% of all associations. They further showed that genetic effects on metabolites, in general, is modified by statin and aging.

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