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Hagenbeek, F.A.; Pool, R.; Dongen, J. van; Draisma, H.H.M.; Hottenga, J.J.; Willemsen, G.; ... ; BBMRI Metabolomics Consortium (2020)

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Article / Letter to editor
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 (h(total)(2)), and the proportion of heritability captured by known metabolite loci (h(Metabolite-hits)(2)) for 309 lipids and 52 organic acids. Our study reveals significant differences in h(Metabolite-hits)(2) among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h(Metabolite-hits)(2) estimates than phosphatidylcholines with low degrees of...Show moreMetabolomics 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 (h(total)(2)), and the proportion of heritability captured by known metabolite loci (h(Metabolite-hits)(2)) for 309 lipids and 52 organic acids. Our study reveals significant differences in h(Metabolite-hits)(2) among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h(Metabolite-hits)(2) 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.Show less
All authors
Hagenbeek, F.A.; Pool, R.; Dongen, J. van; Draisma, H.H.M.; Hottenga, J.J.; Willemsen, G.; Abdellaoui, A.; Fedko, I.O.; Braber, A. den; Visser, P.J.; Geus, E.J.C.N. de; Dijk, K.W. van; Verhoeven, A.; Suchiman, H.E.; Beekman, M.; Slagboom, P.E.; Duijn, C.M. van; Harms, A.C.; Hankemeier, T.; Bartels, M.; Nivard, M.G.; Boomsma, D.I.; Wolf, J.J.H.B.; Cats, D.; Amin, N.; Beulens, J.W.; Bom, J.A. van der; Bomer, N.; Demirkan, A.; Hilten, J.A. van; Meessen, J.M.T.A.; Moed, M.H.; Fu, J.; Onderwater, G.L.J.; Rutters, F.; So-Osman, C.; Flier, W.M. van der; Heijden, A.A.W.A. van der; Spek, A. van der; Asselbergs, F.W.; Boersma, E.; Elders, P.M.; Geleijnse, J.M.; Ikram, M.A.; Kloppenburg, M.; Meulenbelt, I.; Mooijaart, S.P.; Nelissen, R.G.H.H.; Netea, M.G.; Penninx, B.W.J.H.; Stehouwer, C.D.A.; Teunissen, C.E.; Terwindt, G.M.; Hart, L.M. 't; Maagdenberg, A.M.J.M. van den; Harst, P. van der; Horst, I.C.C. van der; Kallen, C.J.H. van der; Greevenbroek, M.M.J. van; Spil, W.E. van; Wijmenga, C.; Zwinderman, A.H.; Zhernikova, A.; Jukema, J.W.; Mei, H.; Slofstra, M.; Swertz, M.; Akker, E.B. van den; Deelen, J.; Reinders, M.J.T.; BBMRI Metabolomics Consortium
Date
2020-01-07
Journal
Nature Communications
Volume
11
Issue
1
DOI
doi:10.1038/s41467-019-13770-6
Link
https://www.nature.com/articles/s41467-019-13770-6