Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
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. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2 Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
|Persistent URL||dx.doi.org/10.1038/s41467-019-13770-6, hdl.handle.net/1765/123740|
Hagenbeek, F.A. (Fiona A.), Pool, R, van Dongen, J, Draisma, G, Hottenga, J.J, Willemsen, G. (Gonneke), … Boomsma, D.I. (2020). Heritability estimates for 361 blood metabolites across 40 genome-wide association studies. Nature Communications, 11(1). doi:10.1038/s41467-019-13770-6