Heritability of Urinary Amines, Organic Acids, and Steroid Hormones in Children

Fiona A. Hagenbeek, Jenny van Dongen, René Pool, Amy C. Harms, Peter J. Roetman, Vassilios Fanos, Britt J. van Keulen, Brian R. Walker, Naama Karu, Hilleke E. Hulshoff Pol, Joost Rotteveel, Martijn J. J. Finken, Robert R. J. M. Vermeiren, Cornelis Kluft, Meike Bartels, Thomas Hankemeier, Dorret I. Boomsma

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Variation in metabolite levels reflects individual differences in genetic and environmental factors. Here, we investigated the role of these factors in urinary metabolomics data in children. We examined the effects of sex and age on 86 metabolites, as measured on three metabolomics platforms that target amines, organic acids, and steroid hormones. Next, we estimated their heritability in a twin cohort of 1300 twins (age range: 5.7–12.9 years). We observed associations between age and 50 metabolites and between sex and 21 metabolites. The monozygotic (MZ) and dizygotic (DZ) correlations for the urinary metabolites indicated a role for non-additive genetic factors for 50 amines, 13 organic acids, and 6 steroids. The average broad-sense heritability for these amines, organic acids, and steroids was 0.49 (range: 0.25–0.64), 0.50 (range: 0.33–0.62), and 0.64 (range: 0.43–0.81), respectively. For 6 amines, 7 organic acids, and 4 steroids the twin correlations indicated a role for shared environmental factors and the average narrow-sense heritability was 0.50 (range: 0.37–0.68), 0.50 (range; 0.23–0.61), and 0.47 (range: 0.32–0.70) for these amines, organic acids, and steroids. We conclude that urinary metabolites in children have substantial heritability, with similar estimates for amines and organic acids, and higher estimates for steroid hormones.
Original languageEnglish
Article number474
Pages (from-to)1-17
Number of pages17
JournalMetabolites
Volume12
Issue number6
Early online date24 May 2022
DOIs
Publication statusPublished - Jun 2022

Bibliographical note

Special Issue: The Intersection of Metabolomics and Genomics and Their Role in Human Health.

Funding

The current work is supported by the \u201CAggression in Children: Unraveling gene-environment interplay to inform Treatment and Intervention strategies\u201D project (ACTION) and the Consortium on Individual Development (CID). ACTION received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no 602768. CID is funded through the Gravitation Program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant number 024-001-003). The Netherlands Twin Register is supported by multiple grants from the Netherlands Organizations for Scientific Research (NWO) and Medical Research (ZonMW): Netherlands Twin Registry Repository (NWO 480-15-001/674); Genetic influences on stability and change in psychopathology from childhood to young adulthood (ZonMw 912-10-020); Twin family database for behavior genomics studies (NWO 480-04-004); Twin research focusing on behavior (NWO 400-05-717); Longitudinal data collection from teachers of Dutch twins and their siblings (NWO 481-08-011), Twin-family-study of individual differences in school achievement (NWO-FES, 056-32-010), Genotype/phenotype database for behavior genetic and genetic epidemiological studies (ZonMw Middelgroot 911-09-032); the Biobank-based integrative omics study (BIOS) funded by BBMRI-NL (NWO projects 184.021.007 and 184.033.111); the European Science Council (ERC) Genetics of Mental Illness (ERC Advanced, 230374, PI Boomsma); Developmental trajectories of psychopathology (NIMH 1RC2 MH089995); the Avera Institute for Human Genetics, Sioux Falls, USA; the Royal Netherlands Academy of Science Professor Award (PAH/6635) to D.I.B. J.v.D. is supported by the NWO-funded X-omics project (184.034.019). M.B. is supported by an ERC consolidator grant (WELL-BEING 771057, PI Bartels). Funding: The current work is supported by the \u201CAggression in Children: Unraveling gene-environment interplay to inform Treatment and Intervention strategies\u201D project (ACTION) and the Consortium on Individual Development (CID). ACTION received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no 602768. CID is funded through the Gravitation Program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant number 024-001-003). The Netherlands Twin Register is supported by multiple grants from the Netherlands Organizations for Scientific Research (NWO) and Medical Research (ZonMW): Netherlands Twin Registry Repository (NWO 480-15-001/674); Genetic influences on stability and change in psychopathology from childhood to young adulthood (ZonMw 912-10-020); Twin family database for behavior genomics studies (NWO 480-04-004); Twin research focusing on behavior (NWO 400-05-717); Longitudinal data collection from teachers of Dutch twins and their siblings (NWO 481-08-011), Twin-family-study of individual differences in school achievement (NWO-FES, 056-32-010), Genotype/phenotype database for behavior genetic and genetic epidemiological studies (ZonMw Middelgroot 911-09-032); the Biobank-based integrative omics study (BIOS) funded by BBMRI-NL (NWO projects 184.021.007 and 184.033.111); the European Science Council (ERC) Genetics of Mental Illness (ERC Advanced, 230374, PI Boomsma); Developmental trajectories of psychopathology (NIMH 1RC2 MH089995); the Avera Institute for Human Genetics, Sioux Falls, USA; the Royal Netherlands Academy of Science Professor Award (PAH/6635) to D.I.B. J.v.D. is supported by the NWO-funded X-omics project (184.034.019). M.B. is supported by an ERC consolidator grant (WELL-BEING 771057, PI Bartels).

FundersFunder number
Avera Institute for Human Genetics, Sioux Falls
BBMRI-NL184.033.111, 184.021.007
Dutch Ministry of Education, Culture, and Science
European Science Council
Genetics of Mental Illness230374
Medical Research
NWO-FESMiddelgroot 911-09-032, 056-32-010
NWO-funded X-omics project184.034.019, WELL-BEING 771057
Netherlands Twin Registry Repository481-08-011, 400-05-717, NWO 480-04-004, 480-15-001/674, 912-10-020
Koninklijke Nederlandse Akademie van Wetenschappen (KNAW)PAH/6635
National Institute of Mental Health1RC2 MH089995
National Institute of Mental Health
Seventh Framework Programme602768
Seventh Framework Programme
ZonMw
Nederlandse Organisatie voor Wetenschappelijk Onderzoek024-001-003
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Seventh Framework Programme

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