TY - JOUR
T1 - Heritability of Urinary Amines, Organic Acids, and Steroid Hormones in Children
AU - Hagenbeek, Fiona A
AU - van Dongen, Jenny
AU - Pool, René
AU - Harms, Amy C
AU - Roetman, Peter J
AU - Fanos, Vassilios
AU - van Keulen, Britt J
AU - Walker, Brian R
AU - Karu, Naama
AU - Hulshoff Pol, Hilleke E
AU - Rotteveel, Joost
AU - Finken, Martijn J J
AU - Vermeiren, Robert R J M
AU - Kluft, Cornelis
AU - Bartels, Meike
AU - Hankemeier, Thomas
AU - Boomsma, Dorret I
N1 - Funding Information:
Funding: The current work is supported by the “Aggression in Children: Unraveling gene-environment interplay to inform Treatment and Intervention strategies” 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).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5/24
Y1 - 2022/5/24
N2 - 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.
AB - 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.
KW - amines
KW - children
KW - classical twin design
KW - heritability
KW - metabolites
KW - organic acids
KW - steroid hormones
KW - urine
UR - http://www.scopus.com/inward/record.url?scp=85131548710&partnerID=8YFLogxK
U2 - 10.3390/metabo12060474
DO - 10.3390/metabo12060474
M3 - Article
C2 - 35736407
SN - 2218-1989
VL - 12
JO - Metabolites
JF - Metabolites
IS - 6
M1 - 474
ER -