The genomic architecture of blood metabolites based on a decade of genome-wide analyses
Hagenbeek F., Pool R., van Dongen J., Draisma HHM., Hottenga JJ., Willemsen G., Abdellaoui A., Fedko I., Braber AD., Visser PJ., de Geus EJCN., van Dijk KW., Verhoeven A., Suchiman E., Beekman M., Slagboom E., van Duijn C., Harms A., Hankemeier T., Bartels M., Nivard M., Boomsma D., BBMRI Metabolomics Consortium None.
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 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.