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. 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.
Original languageEnglish
Article number39
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 2020

Cite this

@article{10eae864577d4bb89562e70f33596306,
title = "Heritability estimates for 361 blood metabolites across 40 genome-wide association studies",
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. 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.",
author = "Hagenbeek, {Fiona A.} and Ren{\'e} Pool and {van Dongen}, Jenny and Draisma, {Harmen H. M.} and {Jan Hottenga}, Jouke and Gonneke Willemsen and Abdel Abdellaoui and Fedko, {Iryna O.} and {den Braber}, Anouk and Visser, {Pieter Jelle} and {de Geus}, {Eco J. C. N.} and {Willems van Dijk}, Ko and Aswin Verhoeven and Suchiman, {H. Eka} and Marian Beekman and Slagboom, {P. Eline} and {van Duijn}, {Cornelia M.} and Barkey Wolf, {J. J. H.} and D. Cats and N. Amin and Beulens, {J. W.} and {van der Bom}, {J. A.} and N. Bomer and A. Demirkan and {van Hilten}, {J. A.} and Meessen, {J. M. T. A.} and Moed, {M. H.} and J. Fu and Onderwater, {G. L. J.} and F. Rutters and C. So-Osman and {van der Flier}, {W. M.} and {van der Heijden}, {A. A. W. A.} and {van der Spek}, A. and Asselbergs, {F. W.} and E. Boersma and Elders, {P. M.} and Penninx, {B. W. J. H.} and Teunissen, {C. E.} and Reinders, {M. J. T.} and {BBMRI Metabolomics Consortium} and Beulens, {J. W.} and F. Rutters and {van der Flier}, {W. M.} and {van der Heijden}, {A. A. W. A.} and {van der Spek}, A. and Elders, {P. M.} and Penninx, {B. W. J. H.} and Teunissen, {C. E.} and {'t Hart}, {L. M.} and Reinders, {M. J. T.}",
year = "2020",
doi = "10.1038/s41467-019-13770-6",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies. / BBMRI Metabolomics Consortium.

In: Nature Communications, Vol. 11, No. 1, 39, 2020.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

AU - Hagenbeek, Fiona A.

AU - Pool, René

AU - van Dongen, Jenny

AU - Draisma, Harmen H. M.

AU - Jan Hottenga, Jouke

AU - Willemsen, Gonneke

AU - Abdellaoui, Abdel

AU - Fedko, Iryna O.

AU - den Braber, Anouk

AU - Visser, Pieter Jelle

AU - de Geus, Eco J. C. N.

AU - Willems van Dijk, Ko

AU - Verhoeven, Aswin

AU - Suchiman, H. Eka

AU - Beekman, Marian

AU - Slagboom, P. Eline

AU - van Duijn, Cornelia M.

AU - Barkey Wolf, J. J. H.

AU - Cats, D.

AU - Amin, N.

AU - Beulens, J. W.

AU - van der Bom, J. A.

AU - Bomer, N.

AU - Demirkan, A.

AU - van Hilten, J. A.

AU - Meessen, J. M. T. A.

AU - Moed, M. H.

AU - Fu, J.

AU - Onderwater, G. L. J.

AU - Rutters, F.

AU - So-Osman, C.

AU - van der Flier, W. M.

AU - van der Heijden, A. A. W. A.

AU - van der Spek, A.

AU - Asselbergs, F. W.

AU - Boersma, E.

AU - Elders, P. M.

AU - Penninx, B. W. J. H.

AU - Teunissen, C. E.

AU - Reinders, M. J. T.

AU - BBMRI Metabolomics Consortium

AU - Beulens, J. W.

AU - Rutters, F.

AU - van der Flier, W. M.

AU - van der Heijden, A. A. W. A.

AU - van der Spek, A.

AU - Elders, P. M.

AU - Penninx, B. W. J. H.

AU - Teunissen, C. E.

AU - 't Hart, L. M.

AU - Reinders, M. J. T.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31911595

U2 - 10.1038/s41467-019-13770-6

DO - 10.1038/s41467-019-13770-6

M3 - Article

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 39

ER -