Year: 2020
Type: 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 and lipid species. We performed a review of all genetic association studies, and identified > 800 class-specific metabolite loci that influence metabolite levels. In a twin-family cohort ( N = 5,117), these metabolite loci were leveraged to simultaneously estimate total heritability ( h 2 total ), and the proportion of heritability captured by known metabolite loci ( h 2 Metabolite-hits ) for 309 lipids and 52 organic acids. Our study revealed significant differences in h 2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation had higher h 2 Metabolite-hits estimates than phosphatidylcholines with a low degree of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes and lipid species.
Source: Nature Communications
Authors: 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. Eka Suchiman, Marian Beekman, P. Eline Slagboom, Cornelia M. van Duijn, J. J. H. Barkey Wolf, D. Cats, N. Amin, 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, L. M. ‘t Hart, A. M. J. M. van den Maagdenberg, P. van der Harst, I. C. C. van der Horst, C. J. H. van der Kallen, M. M. J. van Greevenbroek, W. E. van Spil, C. Wijmenga, A. H. Zwinderman, A. Zhernikova, J. W. Jukema, H. Mei, M. Slofstra, M. Swertz, E. B. van den Akker, J. Deelen, M. J. T. Reinders, Amy C. Harms, Thomas Hankemeier, Meike Bartels, Michel G. Nivard, Dorret I. Boomsma
Institutions: Amsterdam Public Health, Vrije Universiteit Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Neuroscience, Maastricht University, Leiden University Medical Center, Erasmus MC, University Medical Center Utrecht, TIAS School for Business and Society, Tilburg University, Sanquin, Jon J van Rood Centre for Clinical Transfusion Research, University Medical Center Groningen, University of Groningen, Amsterdam UMC Location Vrije Universiteit Amsterdam, Wageningen University & Research, University of Bonn, Radboud University Medical Center, Maastricht University Medical Centre, Amsterdam UMC Location University of Amsterdam, Leiden University, Netherlands Metabolomics Centre, Delft University of Technology, Max Planck Institute for Biology of Ageing
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Funders: Foundation for the National Institutes of Health, European Federation of Pharmaceutical Industries and Associations, European Commission, Universiteit Leiden, Rijksuniversiteit Groningen, Koninklijke Nederlandse Akademie van Wetenschappen, Universiteit van Amsterdam, Technische Universiteit Delft, Vrije Universiteit Amsterdam, Universiteit Maastricht, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Universitair Medisch Centrum Utrecht, Maastricht Universitair Medisch Centrum, Leids Universitair Medisch Centrum, Universitair Medisch Centrum Groningen, Radboud Universitair Medisch Centrum, Universiteit van Tilburg, Rheinische Friedrich-Wilhelms-Universität Bonn, Amsterdam Neuroscience, National Institutes of Health, Wageningen University and Research, Erasmus Universitair Medisch Centrum Rotterdam, CARIM School for Cardiovascular Diseases, Universiteit Maastricht, National Institute of Mental Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1028663679, G1073258374, G126399678, G1389291084, G1447699044, G1545006349, G2748385693, G2861369480, G294002421, G2973790809, BBMRI-NL2.0: The NL-Biobank Research Facility, G300706285, G3121967442, G3207356259, G3404090561, G3444887196, Collaborative Study of Genetics of Dizygotic Twinning, G357049385, G383582915, G393177772, Genomics of Developmental Trajectories in Twins, G4374337615, G4411843255, G4460629988, Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strateg, G4663226093, European Network for Genetic and Genomic Epidemiology, G4921234783, G5468713758, Limited Competition: Continuation of the Center for Genomic Studies on Mental Disorders, G5520316217, G5598020036, G5702163051, G5732418131, G591084189, G6073771368, G6144234142, G6382720711, G6663973959, G6838351527, G695093283, G7206744036, G7229602471, Netherlands Twin Registry Repository: researching the interplay between genome and environment, Netherlands X-omics Initiative, G7655969080, G7680195755, G7924559645, Integration of Genomics & Transcriptomics in Normal Twins & Major Depression, European Medical Information Framework, G8263226176, G84497985, G8662178672, Major Depression: Stage 1 Genomewide Association in Population-Based Samples, G86865590, G8849477942, G9000126205, G9000192955
OpenAlex ID: W2994482524