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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-) s...

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Autores principales: Hagenbeek, Fiona A., Pool, René, 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946682/
https://www.ncbi.nlm.nih.gov/pubmed/31911595
http://dx.doi.org/10.1038/s41467-019-13770-6
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author Hagenbeek, Fiona A.
Pool, René
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.
author_facet Hagenbeek, Fiona A.
Pool, René
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.
author_sort Hagenbeek, Fiona A.
collection PubMed
description 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.
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spelling pubmed-69466822020-01-09 Heritability estimates for 361 blood metabolites across 40 genome-wide association studies Hagenbeek, Fiona A. Pool, René 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. Nat Commun Article 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. Nature Publishing Group UK 2020-01-07 /pmc/articles/PMC6946682/ /pubmed/31911595 http://dx.doi.org/10.1038/s41467-019-13770-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hagenbeek, Fiona A.
Pool, René
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.
Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
title Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
title_full Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
title_fullStr Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
title_full_unstemmed Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
title_short Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
title_sort heritability estimates for 361 blood metabolites across 40 genome-wide association studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946682/
https://www.ncbi.nlm.nih.gov/pubmed/31911595
http://dx.doi.org/10.1038/s41467-019-13770-6
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