The genomic architecture of blood metabolites based on a decade of genome-wide analyses
Hagenbeek, F. A.; Pool, R.; van Dongen, J.; Draisma, H. H. M.; Hottenga, J. J.; Willemsen, G.; Abdellaoui, A.; Fedko, I. O.; den Braber, A.; Visser, P. J.; de Geus, E. J.; Willems van Dijk, K.; Verhoeven, A.; Suchiman, H. E. D.; Beekman, M.; Slagboom, P. E.; van Duijn, C. M.; BBMRI-NL Consortium, ; Harms, A. C.; Hankemeier, T.; Bartels, M.; Nivard, M. G.; Boomsma, D. I.
Show abstract
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 (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study revealed significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation had higher h2Metabolite-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.
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