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Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels

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Title: Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels
Authors: Draisma, HHM
Pool, R
Kobl, M
Jansen, R
Petersen, A-K
Vaarhorst, AAM
Yet, I
Haller, T
Demirkan, A
Esko, T
Zhu, G
Boehringer, S
Beekman, M
Van Klinken, JB
Roemisch-Margl, W
Prehn, C
Adamski, J
De Craen, AJM
Van Leeuwen, EM
Amin, N
Dharuri, H
Westra, H-J
Franke, L
De Geus, EJC
Hottenga, JJ
Willemsen, G
Henders, AK
Montgomery, GW
Nyholt, DR
Whitfield, JB
Penninx, BW
Spector, TD
Metspalu, A
Slagboom, PE
Van Dijk, KW
't Hoen, PAC
Strauch, K
Martin, NG
Van Ommen, G-JB
Illig, T
Bell, JT
Mangino, M
Suhre, K
McCarthy, MI
Gieger, C
Isaacs, A
Van Duijn, CM
Boomsma, DI
Item Type: Journal Article
Abstract: Metabolites are small molecules involved in cellular metabolism, which can be detected in biological samples using metabolomic techniques. Here we present the results of genome-wide association and meta-analyses for variation in the blood serum levels of 129 metabolites as measured by the Biocrates metabolomic platform. In a discovery sample of 7,478 individuals of European descent, we find 4,068 genome- and metabolome-wide significant (Z-test, P<1.09 × 10¯⁹) associations between single-nucleotide polymorphisms (SNPs) and metabolites, involving 59 independent SNPs and 85 metabolites. Five of the fifty-nine independent SNPs are new for serum metabolite levels, and were followed-up for replication in an independent sample (N=1,182). The novel SNPs are located in or near genes encoding metabolite transporter proteins or enzymes (SLC22A16, ARG1, AGPS and ACSL1) that have demonstrated biomedical or pharmaceutical importance. The further characterization of genetic influences on metabolic phenotypes is important for progress in biological and medical research.
Issue Date: 12-Jun-2015
Date of Acceptance: 20-Apr-2015
URI: http://hdl.handle.net/10044/1/58035
DOI: https://dx.doi.org/10.1038/ncomms8208
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 6
Copyright Statement: © 2015 Macmillan Publishers Limited. All rights reserved.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
Genome-Wide Association Study
Polymorphism, Single Nucleotide
MD Multidisciplinary
Publication Status: Published
Article Number: ARTN 7208
Appears in Collections:Department of Medicine (up to 2019)