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

BBMRI Metabolomics Consortium; Fiona A. Hagenbeek; Rene 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. Eka Suchiman; Marian Beekman; P. Eline Slagboom; Cornelia M. van Duijn; Amy C. Harms; Thomas Hankemeier; Meike Bartels; Michel G. Nivard; Dorret I. Boomsma

doi:10.1038/s41467-019-13770-6

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

BBMRI Metabolomics Consortium, Fiona A. Hagenbeek^*, Rene 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. Eka Suchiman, Marian Beekman, P. Eline Slagboom, Cornelia M. van Duijn, Amy C. Harms, Thomas HankemeierMeike Bartels, Michel G. Nivard, Dorret I. Boomsma

^*Corresponding author for this work

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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 language	English
Article number	39
Number of pages	11
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13770-6
Publication status	Published - 7-Jan-2020

Keywords

NETHERLANDS TWIN REGISTER
MISSING HERITABILITY
GENOTYPE IMPUTATION
VARIANCE-ESTIMATION
METABOLOMICS
SELECTION
DATABASE
BIOBANK

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BBMRI Metabolomics Consortium, Hagenbeek, F. A., Pool, R., van Dongen, J., Draisma, H. H. M., Jan Hottenga, J., Willemsen, G., Abdellaoui, A., Fedko, I. O., den Braber, A., Visser, P. J., de Geus, E. J. C. N., Willems van Dijk, K., Verhoeven, A., Suchiman, H. E., Beekman, M., Slagboom, P. E., van Duijn, C. M., Harms, A. C., ... Boomsma, D. I. (2020). Heritability estimates for 361 blood metabolites across 40 genome-wide association studies. Nature Communications, 11(1), Article 39. https://doi.org/10.1038/s41467-019-13770-6

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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.",

keywords = "NETHERLANDS TWIN REGISTER, MISSING HERITABILITY, GENOTYPE IMPUTATION, VARIANCE-ESTIMATION, METABOLOMICS, SELECTION, DATABASE, BIOBANK",

author = "{BBMRI Metabolomics Consortium} and Hagenbeek, {Fiona A.} and Rene 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 Harms, {Amy C.} and Thomas Hankemeier and Meike Bartels and Nivard, {Michel G.} and Boomsma, {Dorret I.} and Wolf, {J. J. H. Barkey} 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 Asselbergs, {F. W.} and E. Boersma and Geleijnse, {J. M.} and Penninx, {B. W. J. H.} and Stehouwer, {C. D. A.} and Teunissen, {C. E.} and {'t Hart}, {L. M.} and {van der Harst}, P. and {van der Horst}, {I. C. C.} and C. Wijmenga and H. Mei and M. Slofstra and M. Swertz and J. Deelen and Reinders, {M. J. T.}",

year = "2020",

month = jan,

day = "7",

doi = "10.1038/s41467-019-13770-6",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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BBMRI Metabolomics Consortium, Hagenbeek, FA, Pool, R, van Dongen, J, Draisma, HHM, Jan Hottenga, J, 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, PE, van Duijn, CM, Harms, AC, Hankemeier, T, Bartels, M, Nivard, MG & Boomsma, DI 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

TY - JOUR

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

AU - BBMRI Metabolomics Consortium

AU - Hagenbeek, Fiona A.

AU - Pool, Rene

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 - Harms, Amy C.

AU - Hankemeier, Thomas

AU - Bartels, Meike

AU - Nivard, Michel G.

AU - Boomsma, Dorret I.

AU - Wolf, J. J. H. Barkey

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 - Asselbergs, F. W.

AU - Boersma, E.

AU - Geleijnse, J. M.

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

AU - Stehouwer, C. D. A.

AU - Teunissen, C. E.

AU - 't Hart, L. M.

AU - van der Harst, P.

AU - van der Horst, I. C. C.

AU - Wijmenga, C.

AU - Mei, H.

AU - Slofstra, M.

AU - Swertz, M.

AU - Deelen, J.

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.

KW - NETHERLANDS TWIN REGISTER

KW - MISSING HERITABILITY

KW - GENOTYPE IMPUTATION

KW - VARIANCE-ESTIMATION

KW - METABOLOMICS

KW - SELECTION

KW - DATABASE

KW - BIOBANK

U2 - 10.1038/s41467-019-13770-6

DO - 10.1038/s41467-019-13770-6

M3 - Article

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 39

ER -

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

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Keywords

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