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

Fiona A. Hagenbeek*, René Pool, Jenny van Dongen, Harmen H.M. Draisma, Jouke Jan Hottenga, Gonneke Willemsen, Abdel Abdellaoui, Iryna O. Fedko, Anouk den Braber, Pieter Jelle Visser, Eco J.C.N. de Geus, Ko Willems van Dijk, Aswin Verhoeven, H.E. Suchiman, Marian Beekman, Eline P. Slagboom, Cornelia M. van Duijn, J.J.H. Barkey Wolf, D. Cats, N. Amin & 30 others J.W. Beulens, J.A. van der Bom, N. Bomer, A. Demirkan, J.A. van Hilten, J.M.T.A. Meessen, M.H. Moed, J. Fu, G.L.J. Onderwater, F. Rutters, C. So-Osman, W.M. van der Flier, A.A.W.A. van der Heijden, A. van der Spek, F.W. Asselbergs, E. Boersma, P.M. Elders, J.M. Geleijnse, M.A. Ikram, M. Kloppenburg, I. Meulenbelt, S.P. Mooijaart, R.G.H.H. Nelissen, M.G. Netea, B.W.J.H. Penninx, C.D.A. Stehouwer, C.E. Teunissen, G.M. Terwindt, J.W. Jukema, M.J.T. Reinders

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 - 7 Jan 2020

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genome
metabolites
Genome-Wide Association Study
Metabolites
Phosphatidylcholines
blood
Blood
Genes
Exome
Lipids
Acids
Metabolomics
estimates
Genome
loci
Organic acids
lipids
acids
sequencing
metabolism

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Hagenbeek, F. A., Pool, R., van Dongen, J., Draisma, H. H. M., Hottenga, J. J., Willemsen, G., ... Reinders, M. J. T. (2020). Heritability estimates for 361 blood metabolites across 40 genome-wide association studies. Nature Communications, 11(1), [39]. https://doi.org/10.1038/s41467-019-13770-6
Hagenbeek, Fiona A. ; Pool, René ; van Dongen, Jenny ; Draisma, Harmen H.M. ; Hottenga, Jouke Jan ; Willemsen, Gonneke ; Abdellaoui, Abdel ; Fedko, Iryna O. ; den Braber, Anouk ; Visser, Pieter Jelle ; de Geus, Eco J.C.N. ; Willems van Dijk, Ko ; Verhoeven, Aswin ; Suchiman, H.E. ; Beekman, Marian ; Slagboom, Eline P. ; van Duijn, Cornelia M. ; Barkey Wolf, J.J.H. ; Cats, D. ; Amin, N. ; Beulens, J.W. ; van der Bom, J.A. ; Bomer, N. ; Demirkan, A. ; van Hilten, J.A. ; Meessen, J.M.T.A. ; Moed, M.H. ; Fu, J. ; Onderwater, G.L.J. ; Rutters, F. ; So-Osman, C. ; van der Flier, W.M. ; van der Heijden, A.A.W.A. ; van der Spek, A. ; 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. ; Jukema, J.W. ; Reinders, M.J.T. / Heritability estimates for 361 blood metabolites across 40 genome-wide association studies. In: Nature Communications. 2020 ; Vol. 11, No. 1.
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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 Hottenga, {Jouke Jan} 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 H.E. Suchiman and Marian Beekman and Slagboom, {Eline P.} and {van Duijn}, {Cornelia M.} and J.J.H. Barkey Wolf and D. Cats and N. Amin and J.W. Beulens and {van der Bom}, J.A. and N. Bomer and A. Demirkan and {van Hilten}, J.A. and J.M.T.A. Meessen and M.H. Moed and J. Fu and G.L.J. Onderwater 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 F.W. Asselbergs and E. Boersma and P.M. Elders and J.M. Geleijnse and M.A. Ikram and M. Kloppenburg and I. Meulenbelt and S.P. Mooijaart and R.G.H.H. Nelissen and M.G. Netea and B.W.J.H. Penninx and C.D.A. Stehouwer and C.E. Teunissen and G.M. Terwindt and J.W. Jukema and M.J.T. Reinders",
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Hagenbeek, FA, Pool, R, van Dongen, J, Draisma, HHM, Hottenga, JJ, Willemsen, G, Abdellaoui, A, Fedko, IO, den Braber, A, Visser, PJ, de Geus, EJCN, Willems van Dijk, K, Verhoeven, A, Suchiman, HE, Beekman, M, Slagboom, EP, van Duijn, CM, Barkey Wolf, JJH, Cats, D, Amin, N, Beulens, JW, van der Bom, JA, Bomer, N, Demirkan, A, van Hilten, JA, Meessen, JMTA, Moed, MH, Fu, J, Onderwater, GLJ, Rutters, F, So-Osman, C, van der Flier, WM, van der Heijden, AAWA, van der Spek, A, Asselbergs, FW, Boersma, E, Elders, PM, Geleijnse, JM, Ikram, MA, Kloppenburg, M, Meulenbelt, I, Mooijaart, SP, Nelissen, RGHH, Netea, MG, Penninx, BWJH, Stehouwer, CDA, Teunissen, CE, Terwindt, GM, Jukema, JW & Reinders, MJT 2020, 'Heritability estimates for 361 blood metabolites across 40 genome-wide association studies', Nature Communications, vol. 11, no. 1, 39. https://doi.org/10.1038/s41467-019-13770-6

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies. / Hagenbeek, Fiona A.; Pool, René; van Dongen, Jenny; Draisma, Harmen H.M.; Hottenga, Jouke Jan; Willemsen, Gonneke; Abdellaoui, Abdel; Fedko, Iryna O.; den Braber, Anouk; Visser, Pieter Jelle; de Geus, Eco J.C.N.; Willems van Dijk, Ko; Verhoeven, Aswin; Suchiman, H.E.; Beekman, Marian; Slagboom, Eline P.; van Duijn, Cornelia M.; Barkey Wolf, J.J.H.; Cats, D.; Amin, N.; Beulens, J.W.; van der Bom, J.A.; Bomer, N.; Demirkan, A.; van Hilten, J.A.; Meessen, J.M.T.A.; Moed, M.H.; Fu, J.; Onderwater, G.L.J.; Rutters, F.; So-Osman, C.; van der Flier, W.M.; van der Heijden, A.A.W.A.; van der Spek, A.; 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.; Jukema, J.W.; Reinders, M.J.T.

In: Nature Communications, Vol. 11, No. 1, 39, 07.01.2020.

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 - Hottenga, Jouke Jan

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.E.

AU - Beekman, Marian

AU - Slagboom, Eline P.

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 - Geleijnse, J.M.

AU - Ikram, M.A.

AU - Kloppenburg, M.

AU - Meulenbelt, I.

AU - Mooijaart, S.P.

AU - Nelissen, R.G.H.H.

AU - Netea, M.G.

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

AU - Stehouwer, C.D.A.

AU - Teunissen, C.E.

AU - Terwindt, G.M.

AU - Jukema, J.W.

AU - Reinders, M.J.T.

PY - 2020/1/7

Y1 - 2020/1/7

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.

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 -

Hagenbeek FA, Pool R, van Dongen J, Draisma HHM, Hottenga JJ, Willemsen G et al. Heritability estimates for 361 blood metabolites across 40 genome-wide association studies. Nature Communications. 2020 Jan 7;11(1). 39. https://doi.org/10.1038/s41467-019-13770-6