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

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 pro... Mehr ...

Verfasser: Hagenbeek, Fiona A.
Pool, Rene
van Dongen, Jenny
Draisma, Harmen H. M.
Jan Hottenga, Jouke
Willemsen, Gonneke
Abdellaoui, Abdel
Fedko, Iryna O.
den Braber, Anouk
Visser, Pieter Jelle
de Geus, Eco J. C. N.
Willems van Dijk, Ko
Verhoeven, Aswin
Suchiman, H. Eka
Beekman, Marian
Slagboom, P. Eline
van Duijn, Cornelia M.
Harms, Amy C.
Hankemeier, Thomas
Bartels, Meike
Nivard, Michel G.
Boomsma, Dorret I.
Wolf, J. J. H. Barkey
Cats, D.
Amin, N.
Beulens, J. W.
van der Bom, J. A.
Bomer, N.
Demirkan, A.
van Hilten, J. A.
Meessen, J. M. T. A.
Moed, M. H.
Fu, J.
Onderwater, G. L. J.
Rutters, F.
So-Osman, C.
van der Flier, W. M.
van der Heijden, A. A. W. A.
van der Spek, A.
Asselbergs, F. W.
Boersma, E.
Elders, P. M.
Geleijnse, J. M.
Nelissen, R. G. H. H.
Stehouwer, C. D. A.
Teunissen, C. E.
van der Horst, I. C. C.
van der Kallen, C. J. H.
van Greevenbroek, M. M. J.
Reinders, M. J. T.
Dokumenttyp: Artikel
Erscheinungsdatum: 2020
Reihe/Periodikum: Hagenbeek , F A , Pool , R , van Dongen , J , Draisma , H H M , Jan Hottenga , J , Willemsen , G , Abdellaoui , A , Fedko , I O , den Braber , A , Visser , P J , de Geus , E J C N , Willems van Dijk , K , Verhoeven , A , Suchiman , H E , Beekman , M , Slagboom , P E , van Duijn , C M , 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 , van der Bom , J A , Bomer , N , Demirkan , A , van Hilten , J A , Meessen , J M T A , Moed , M H , Fu , J , Onderwater , G L J , Rutters , F , So-Osman , C , van der Flier , W M , van der Heijden , A A W A , van der Spek , A , Asselbergs , F W , Boersma , E , Elders , P M , Geleijnse , J M , Nelissen , R G H H , Stehouwer , C D A , Teunissen , C E , van der Horst , I C C , van der Kallen , C J H , van Greevenbroek , M M J , Reinders , M J T & BBMRI Metabolomics Consortium 2020 , ' Heritability estimates for 361 blood metabolites across 40 genome-wide association studies ' , Nature Communications , vol. 11 , no. 1 , 39 . https://doi.org/10.1038/s41467-019-13770-6
Schlagwörter: NETHERLANDS TWIN REGISTER / MISSING HERITABILITY / GENOTYPE IMPUTATION / VARIANCE-ESTIMATION / METABOLOMICS / SELECTION / DATABASE / BIOBANK
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29187560
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://cris.maastrichtuniversity.nl/en/publications/c340eb69-fc02-4639-a40d-b44f4d3116e9

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.