1. Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
- Author
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Hagenbeek, F.A., Pool, R., Dongen, J. van, Draisma, H.H.M., Hottenga, J.J., Willemsen, G., Abdellaoui, A., Fedko, I.O., Braber, A. den, Visser, P.J., Geus, E.J.C.N. de, Dijk, K.W. van, Verhoeven, A., Suchiman, H.E., Beekman, M., Slagboom, P.E., Duijn, C.M. van, Harms, A.C., Hankemeier, T., Bartels, M., Nivard, M.G., Boomsma, D.I., Wolf, J.J.H.B., Cats, D., Amin, N., Beulens, J.W., Bom, J.A. van der, Bomer, N., Demirkan, A., Hilten, J.A. van, Meessen, J.M.T.A., Moed, M.H., Fu, J., Onderwater, G.L.J., Rutters, F., So-Osman, C., Flier, W.M. van der, Heijden, A.A.W.A. van der, Spek, A. van der, 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., Hart, L.M. 't, Maagdenberg, A.M.J.M. van den, Harst, P. van der, Horst, I.C.C. van der, Kallen, C.J.H. van der, Greevenbroek, M.M.J. van, Spil, W.E. van, Wijmenga, C., Zwinderman, A.H., Zhernikova, A., Jukema, J.W., Mei, H., Slofstra, M., Swertz, M., Akker, E.B. van den, Deelen, J., Reinders, M.J.T., BBMRI Metabolomics Consortium, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Cardiovascular Centre (CVC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Neurology, Epidemiology and Data Science, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, General practice, APH - Methodology, Amsterdam Reproduction & Development (AR&D), APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, Laboratory Medicine, Other Research, APH - Aging & Later Life, APH - Personalized Medicine, APH - Digital Health, ACS - Diabetes & metabolism, Adult Psychiatry, Epidemiology, Cardiology, Radiology & Nuclear Medicine, Biological Psychology, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), Interne Geneeskunde, MUMC+: Centrum voor Chronische Zieken (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), MUMC+: MA Endocrinologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Hematologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Reumatologie (9), and RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome
- Subjects
Netherlands Twin Register (NTR) ,0301 basic medicine ,SELECTION ,Quantitative trait loci ,Nutrition and Disease ,DATABASE ,Metabolite ,Science ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,General Physics and Astronomy ,Genome-wide association study ,VARIANCE-ESTIMATION ,Biology ,Quantitative trait locus ,GENOTYPE IMPUTATION ,METABOLOMICS ,BIOBANK ,Genome-wide association studies ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,All institutes and research themes of the Radboud University Medical Center ,Missing heritability problem ,MISSING HERITABILITY ,Voeding en Ziekte ,Genetic variation ,Life Science ,NETHERLANDS TWIN REGISTER ,lcsh:Science ,VLAG ,Genetics ,Multidisciplinary ,General Chemistry ,Heritability ,Genetic architecture ,030104 developmental biology ,chemistry ,Lipidomics ,lcsh:Q ,030217 neurology & neurosurgery - 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 (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-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., Blood metabolite levels are under the influence of environmental and genetic factors. Here, Hagenbeek et al. perform heritability estimations for metabolite measures and determine the contribution of known metabolite loci to metabolite levels using data from 40 genome-wide association studies.
- Published
- 2020