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

Fiona A. Hagenbeek; René Pool; Jenny van Dongen; Harmen H. M. Draisma; Jouke‐Jan Hottenga; Gonneke A. H. M. Willemsen; Abdel Abdellaoui; Iryna O. Fedko; Anouk den Braber; Pieter Jelle Visser; Eco J. C. de Geus; Ko Willems van Dijk; Aswin Verhoeven; H. Eka D. Suchiman; Marian Beekman; P. Eline Slagboom; Cornelia M. van Duijn; Amy C. Harms; Thomas Hankemeier; Meike Bartels; Michel Guillaume Nivard; Dorret Irene Boomsma

doi:10.1101/661769

GeneticsbioRxivOct 11, 2019

Preprint

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

Fiona A. Hagenbeek iD, René Pool iD, Jenny van Dongen iD, Harmen H. M. Draisma iD, Jouke‐Jan Hottenga iD, Gonneke A. H. M. Willemsen iD, Abdel Abdellaoui iD, Iryna O. Fedko iD, Anouk den Braber iD, Pieter Jelle Visser iD, Eco J. C. de Geus iD, Ko Willems van Dijk iD, Aswin Verhoeven iD, H. Eka D. Suchiman iD, Marian Beekman iD, P. Eline Slagboom iD, Cornelia M. van Duijn iD, Amy C. Harms iD, Thomas Hankemeier iD, Meike Bartels iD, Michel Guillaume Nivard iD, Dorret Irene Boomsma iD

PDF DOI

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.