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Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes and lipid species. From the literature we aggregate > 800 class-specific metabolite loci that influence metabolite levels. In a twin-family cohort ( N = 5,117) these metabolite loci were leveraged to simultaneously estimate total heritability ( h2total ), SNP-based heritability ( h2SNP ) and the proportion of heritability captured by known metabolite loci ( h2GW-loci ) for 309 lipids and 52 organic acids. Our study revealed significant differences in h2SNP and h2GW-loci among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a higher degree of unsaturation had higher h2GW-loci estimates. This study highlights the importance of common genetic variants for metabolite levels and elucidates the genetic architecture of metabolite classes and lipid species.

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