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

Autor:	Hagenbeek FA; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. f.a.hagenbeek@vu.nl.; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands. f.a.hagenbeek@vu.nl., Pool R; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands., van Dongen J; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands., Draisma HHM; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Jan Hottenga J; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Willemsen G; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Abdellaoui A; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Fedko IO; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., den Braber A; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Alzheimer Center Amsterdam, Department of Neurology, VU Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Amsterdam, The Netherlands., Visser PJ; Alzheimer Center Amsterdam, Department of Neurology, VU Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands., de Geus EJCN; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Amsterdam, The Netherlands., Willems van Dijk K; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.; Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands., Verhoeven A; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., Suchiman HE; Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., Beekman M; Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., Slagboom PE; Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., van Duijn CM; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands., Harms AC; Division of Analytical Biosciences, Leiden Academic Center for Drug Research, Leiden University and The Netherlands Metabolomics Centre, Leiden, The Netherlands., Hankemeier T; Division of Analytical Biosciences, Leiden Academic Center for Drug Research, Leiden University and The Netherlands Metabolomics Centre, Leiden, The Netherlands., Bartels M; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Amsterdam, The Netherlands., Nivard MG; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. m.g.nivard@vu.nl.; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands. m.g.nivard@vu.nl.; Amsterdam Neuroscience, Amsterdam, The Netherlands. m.g.nivard@vu.nl., Boomsma DI; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. di.boomsma@vu.nl.; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands. di.boomsma@vu.nl.; Amsterdam Neuroscience, Amsterdam, The Netherlands. di.boomsma@vu.nl.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Jan 07; Vol. 11 (1), pp. 39. Date of Electronic Publication: 2020 Jan 07.
DOI:	10.1038/s41467-019-13770-6
Abstrakt:	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 (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 reveals significant differences in h 2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h 2 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.
Databáze:	MEDLINE
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