The genomic architecture of blood metabolites based on a decade of genome-wide analyses
Jenny van Dongen,
Harmen H.M. Draisma,
Iryna O. Fedko,
Anouk den Braber,
Pieter Jelle Visser,
Eco JC de Geus,
Ko Willems van Dijk,
H. Eka Suchiman,
P Eline Slagboom,
Cornelia Van Duijn,
BBMRI Metabolomics Consortium,
Michel G. Nivard,
Dorret I Boomsma
Posted 14 Jun 2019
bioRxiv DOI: 10.1101/661769
Posted 14 Jun 2019
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  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. : #ref-2
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