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. We performed a review of all genetic association studies, and identified > 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 ( h  2  total ), and the proportion of heritability captured by known metabolite loci ( h [2][1] Metabolite-hits ) for 309 lipids and 52 organic acids. Our study revealed significant differences in h  2  Metabolite-hits  among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation had higher h  2  Metabolite-hits  estimates than phosphatidylcholines with a low degree of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes and lipid species. [1]: #ref-2

The genomic architecture of blood metabolites based on a decade of genome-wide analyses