TY - JOUR
T1 - Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
AU - Hagenbeek, Fiona A.
AU - Pool, Rene
AU - van Dongen, Jenny
AU - Draisma, Harmen H. M.
AU - Jan Hottenga, Jouke
AU - Willemsen, Gonneke
AU - Abdellaoui, Abdel
AU - Fedko, Iryna O.
AU - den Braber, Anouk
AU - Visser, Pieter Jelle
AU - de Geus, Eco J. C. N.
AU - Willems van Dijk, Ko
AU - Verhoeven, Aswin
AU - Suchiman, H. Eka
AU - Beekman, Marian
AU - Slagboom, P. Eline
AU - van Duijn, Cornelia M.
AU - Harms, Amy C.
AU - Hankemeier, Thomas
AU - Bartels, Meike
AU - Nivard, Michel G.
AU - Boomsma, Dorret I.
AU - Wolf, J. J. H. Barkey
AU - Cats, D.
AU - Amin, N.
AU - Beulens, J. W.
AU - van der Bom, J. A.
AU - Bomer, N.
AU - Demirkan, A.
AU - van Hilten, J. A.
AU - Meessen, J. M. T. A.
AU - Moed, M. H.
AU - Fu, J.
AU - Onderwater, G. L. J.
AU - Rutters, F.
AU - So-Osman, C.
AU - van der Flier, W. M.
AU - van der Heijden, A. A. W. A.
AU - van der Spek, A.
AU - Asselbergs, F. W.
AU - Boersma, E.
AU - Elders, P. M.
AU - Geleijnse, J. M.
AU - Nelissen, R. G. H. H.
AU - Stehouwer, C. D. A.
AU - Teunissen, C. E.
AU - van der Horst, I. C. C.
AU - van der Kallen, C. J. H.
AU - van Greevenbroek, M. M. J.
AU - Reinders, M. J. T.
AU - BBMRI Metabolomics Consortium
PY - 2020/1/7
Y1 - 2020/1/7
N2 - 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(total)(2)), and the proportion of heritability captured by known metabolite loci (h(Metabolite-hits)(2)) for 309 lipids and 52 organic acids. Our study reveals significant differences in h(Metabolite-hits)(2) among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h(Metabolite-hits)(2) 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.
AB - 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(total)(2)), and the proportion of heritability captured by known metabolite loci (h(Metabolite-hits)(2)) for 309 lipids and 52 organic acids. Our study reveals significant differences in h(Metabolite-hits)(2) among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h(Metabolite-hits)(2) 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.
KW - NETHERLANDS TWIN REGISTER
KW - MISSING HERITABILITY
KW - GENOTYPE IMPUTATION
KW - VARIANCE-ESTIMATION
KW - METABOLOMICS
KW - SELECTION
KW - DATABASE
KW - BIOBANK
U2 - 10.1038/s41467-019-13770-6
DO - 10.1038/s41467-019-13770-6
M3 - Article
C2 - 31911595
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 39
ER -