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

HHM Draisma; R Pool; M Kobl; R Jansen; AK Petersen; AAM Vaarhorst; I Yet; T Haller; Ayse Demirkan; T Esko; G Zhu; S Boehringer; M Beekman; JB van Klinken; W Roemisch-Margl; C Prehn; J Adamski; AJM de Craen; Elisa Leeuwen; Najaf Amin; H Dharuri; HJ Westra; L Franke; EJC de Geus; JJ (Jouke Jan) Hottenga; G Willemsen; AK Henders; GW Montgomery; DR Nyholt; JB Whitfield; BW Penninx; TD Spector; A Metspalu; PE (Eline) Slagboom; KW van Dijk; PAC 't Hoen; K Strauch; NG Martin; GJB van Ommen; T Illig; JT Bell; M Mangino; K Suhre; MI McCarthy; C Gieger; Aaron Isaacs; Cornelia Duijn; DI Boomsma

doi:10.1038/ncomms8208

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

HHM Draisma, R Pool, M Kobl, R Jansen, AK Petersen, AAM Vaarhorst, I Yet, T Haller, Ayse Demirkan, T Esko, G Zhu, S Boehringer, M Beekman, JB van Klinken, W Roemisch-Margl, C Prehn, J Adamski, AJM de Craen, Elisa Leeuwen, Najaf AminH Dharuri, HJ Westra, L Franke, EJC de Geus, JJ (Jouke Jan) Hottenga, G Willemsen, AK Henders, GW Montgomery, DR Nyholt, JB Whitfield, BW Penninx, TD Spector, A Metspalu, PE (Eline) Slagboom, KW van Dijk, PAC 't Hoen, K Strauch, NG Martin, GJB van Ommen, T Illig, JT Bell, M Mangino, K Suhre, MI McCarthy, C Gieger, Aaron Isaacs, Cornelia Duijn, DI Boomsma

Research output: Contribution to journal › Article › Academic › peer-review

144 Citations (Scopus)

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 x 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.

Original language	Undefined/Unknown
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8208
Publication status	Published - 2015

Research programs

EMC NIHES-01-64-02

Access to Document

10.1038/ncomms8208

http://hdl.handle.net/1765/85080

Cite this

Draisma, HHM., Pool, R., Kobl, M., Jansen, R., Petersen, AK., 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., Leeuwen, E., ... Boomsma, DI. (2015). Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels. Nature Communications, 6. https://doi.org/10.1038/ncomms8208

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

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 x 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.",

author = "HHM Draisma and R Pool and M Kobl and R Jansen and AK Petersen and AAM Vaarhorst and I Yet and T Haller and Ayse Demirkan and T Esko and G Zhu and S Boehringer and M Beekman and {van Klinken}, JB and W Roemisch-Margl and C Prehn and J Adamski and {de Craen}, AJM and Elisa Leeuwen and Najaf Amin and H Dharuri and HJ Westra and L Franke and {de Geus}, EJC and Hottenga, {JJ (Jouke Jan)} and G Willemsen and AK Henders and GW Montgomery and DR Nyholt and JB Whitfield and BW Penninx and TD Spector and A Metspalu and Slagboom, {PE (Eline)} and {van Dijk}, KW and {'t Hoen}, PAC and K Strauch and NG Martin and {van Ommen}, GJB and T Illig and JT Bell and M Mangino and K Suhre and MI McCarthy and C Gieger and Aaron Isaacs and Cornelia Duijn and DI Boomsma",

year = "2015",

doi = "10.1038/ncomms8208",

language = "Undefined/Unknown",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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Draisma, HHM, Pool, R, Kobl, M, Jansen, R, Petersen, AK, 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, Leeuwen, E, Amin, N, Dharuri, H, Westra, HJ, 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, GJB, Illig, T, Bell, JT, Mangino, M, Suhre, K, McCarthy, MI, Gieger, C, Isaacs, A, Duijn, C & Boomsma, DI 2015, 'Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels', Nature Communications, vol. 6. https://doi.org/10.1038/ncomms8208

TY - JOUR

T1 - Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels

AU - Draisma, HHM

AU - Pool, R

AU - Kobl, M

AU - Jansen, R

AU - Petersen, AK

AU - Vaarhorst, AAM

AU - Yet, I

AU - Haller, T

AU - Demirkan, Ayse

AU - Esko, T

AU - Zhu, G

AU - Boehringer, S

AU - Beekman, M

AU - van Klinken, JB

AU - Roemisch-Margl, W

AU - Prehn, C

AU - Adamski, J

AU - de Craen, AJM

AU - Leeuwen, Elisa

AU - Amin, Najaf

AU - Dharuri, H

AU - Westra, HJ

AU - Franke, L

AU - de Geus, EJC

AU - Hottenga, JJ (Jouke Jan)

AU - Willemsen, G

AU - Henders, AK

AU - Montgomery, GW

AU - Nyholt, DR

AU - Whitfield, JB

AU - Penninx, BW

AU - Spector, TD

AU - Metspalu, A

AU - Slagboom, PE (Eline)

AU - van Dijk, KW

AU - 't Hoen, PAC

AU - Strauch, K

AU - Martin, NG

AU - van Ommen, GJB

AU - Illig, T

AU - Bell, JT

AU - Mangino, M

AU - Suhre, K

AU - McCarthy, MI

AU - Gieger, C

AU - Isaacs, Aaron

AU - Duijn, Cornelia

AU - Boomsma, DI

PY - 2015

Y1 - 2015

N2 - 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 x 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.

AB - 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 x 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.

U2 - 10.1038/ncomms8208

DO - 10.1038/ncomms8208

M3 - Article

C2 - 26068415

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

ER -