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

Harmen H.M. Draisma; René Pool; Michael Kobl; Rick Jansen; Ann Kristin Petersen; Anika A.M. Vaarhorst; Idil Yet; Toomas Haller; Ayşe Demirkan; Tõnu Esko; Gu Zhu; Stefan Böhringer; Marian Beekman; Jan Bert Van Klinken; Werner Römisch-Margl; Cornelia Prehn; Jerzy Adamski; Anton J.M. De Craen; Elisabeth M. Van Leeuwen; Najaf Amin; Harish Dharuri; Harm Jan Westra; Lude Franke; Eco J.C. De Geus; Jouke Jan Hottenga; Gonneke Willemsen; Anjali K. Henders; Grant W. Montgomery; Dale R. Nyholt; John B. Whitfield; Brenda W. Penninx; Tim D. Spector; Andres Metspalu; P. Eline Slagboom; Ko Willems Van Dijk; Peter A.C. 'T Hoen; Konstantin Strauch; Nicholas G. Martin; Gert Jan B. Van Ommen; Thomas Illig; Jordana T. Bell; Massimo Mangino; Karsten Suhre; Mark I. McCarthy; Christian Gieger; Aaron Isaacs; Cornelia M. Van Duijn; Dorret I. Boomsma

doi:10.1038/ncomms8208

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

Harmen H.M. Draisma^*
, René Pool
, Michael Kobl
, Rick Jansen
, Ann Kristin Petersen
, Anika A.M. Vaarhorst
, Idil Yet
, Toomas Haller
, Ayşe Demirkan
, Tõnu Esko
, Gu Zhu
, Stefan Böhringer
, Marian Beekman
, Jan Bert Van Klinken
, Werner Römisch-Margl
, Cornelia Prehn
, Jerzy Adamski
, Anton J.M. De Craen
, Elisabeth M. Van Leeuwen
, Najaf Amin

Harish Dharuri, Harm Jan Westra, Lude Franke, Eco J.C. De Geus, Jouke Jan Hottenga, Gonneke Willemsen, Anjali K. Henders, Grant W. Montgomery, Dale R. Nyholt, John B. Whitfield, Brenda W. Penninx, Tim D. Spector, Andres Metspalu, P. Eline Slagboom, Ko Willems Van Dijk, Peter A.C. 'T Hoen, Konstantin Strauch, Nicholas G. Martin, Gert Jan B. Van Ommen, Thomas Illig, Jordana T. Bell, Massimo Mangino, Karsten Suhre, Mark I. McCarthy, Christian Gieger, Aaron Isaacs, Cornelia M. Van Duijn, Dorret I. Boomsma

^*Corresponding author for this work

Department of Biological Psychology
Vrije Universiteit Amsterdam
VU University Medical Center
Neuroscience Campus Amsterdam
BBMRINL: Infrastructure for the Application of Metabolomics Technology in Epidemiology
Institute of Genetic Epidemiology
Helmholtz Zentrum München - German Research Center for Environmental Health
Department of Psychiatry
Molecular Epidemiology
Leiden University
Netherlands Consortium for Healthy Ageing
Department of Twin Research and Genetic Epidemiology
King's College London
University of Tartu
Department of Epidemiology
Erasmus University Rotterdam
Divisions of Genetics and Endocrinology
Boston Children's Hospital
Medical and Population Genetics
Broad Institute
Department of Genetics
Harvard University
Department of Genetics and Computational Biology
Queensland Institute of Medical Research
Department of Medical Statistics and Bioinformatics
Institute of Bioinformatics and Systems Biology
Institute of Experimental Genetics
Technical University of Munich
Department of Gerontology and Geriatrics
Department of Genetics
University of Groningen
Statistical and Genomic Epidemiology Laboratory
Queensland University of Technology
Department of Endocrinology
Institute of Medical Informatics
Ludwig Maximilian University of Munich
Research Unit of Molecular Epidemiology
Helmholtz ZentrumMünchen
Hannover Medical School
Institute for Human Genetics
Faculty of Biology
Department of Physiology and Biophysics
Qatar Foundation HQ
University of Oxford
Oxford Centre for Diabetes
Oxford National Institute for Health Research Biomedical Research Centre
Institute of Epidemiology II

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

169 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 × 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	English
Article number	7208
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8208
Publication status	Published - 12 Jun 2015
Externally published	Yes

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Draisma, H. H. M., Pool, R., Kobl, M., Jansen, R., Petersen, A. K., Vaarhorst, A. A. M., Yet, I., Haller, T., Demirkan, A., Esko, T., Zhu, G., Böhringer, S., Beekman, M., Van Klinken, J. B., Römisch-Margl, W., Prehn, C., Adamski, J., De Craen, A. J. M., Van Leeuwen, E. M., ... Boomsma, D. I. (2015). Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels. Nature Communications , 6, Article 7208. https://doi.org/10.1038/ncomms8208

@article{7a1f2e54ae49450ca9ac71c365028a12,

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 {\texttimes} 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 = "Draisma, \{Harmen H.M.\} and Ren{\'e} Pool and Michael Kobl and Rick Jansen and Petersen, \{Ann Kristin\} and Vaarhorst, \{Anika A.M.\} and Idil Yet and Toomas Haller and Ay{\c s}e Demirkan and T{\~o}nu Esko and Gu Zhu and Stefan B{\"o}hringer and Marian Beekman and \{Van Klinken\}, \{Jan Bert\} and Werner R{\"o}misch-Margl and Cornelia Prehn and Jerzy Adamski and \{De Craen\}, \{Anton J.M.\} and \{Van Leeuwen\}, \{Elisabeth M.\} and Najaf Amin and Harish Dharuri and Westra, \{Harm Jan\} and Lude Franke and \{De Geus\}, \{Eco J.C.\} and Hottenga, \{Jouke Jan\} and Gonneke Willemsen and Henders, \{Anjali K.\} and Montgomery, \{Grant W.\} and Nyholt, \{Dale R.\} and Whitfield, \{John B.\} and Penninx, \{Brenda W.\} and Spector, \{Tim D.\} and Andres Metspalu and \{Eline Slagboom\}, P. and \{Van Dijk\}, \{Ko Willems\} and \{'T Hoen\}, \{Peter A.C.\} and Konstantin Strauch and Martin, \{Nicholas G.\} and \{Van Ommen\}, \{Gert Jan B.\} and Thomas Illig and Bell, \{Jordana T.\} and Massimo Mangino and Karsten Suhre and McCarthy, \{Mark I.\} and Christian Gieger and Aaron Isaacs and \{Van Duijn\}, \{Cornelia M.\} and Boomsma, \{Dorret I.\}",

year = "2015",

month = jun,

day = "12",

doi = "10.1038/ncomms8208",

language = "English",

volume = "6",

journal = "Nature Communications ",

issn = "2041-1723",

}

Draisma, HHM, Pool, R, Kobl, M, Jansen, R, Petersen, AK, Vaarhorst, AAM, Yet, I, Haller, T, Demirkan, A, Esko, T, Zhu, G, Böhringer, S, Beekman, M, Van Klinken, JB, Römisch-Margl, W, Prehn, C, Adamski, J, De Craen, AJM, Van Leeuwen, EM, 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, Eline Slagboom, P, 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, Van Duijn, CM & Boomsma, DI 2015, 'Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels', Nature Communications , vol. 6, 7208. 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, Harmen H.M.

AU - Pool, René

AU - Kobl, Michael

AU - Jansen, Rick

AU - Petersen, Ann Kristin

AU - Vaarhorst, Anika A.M.

AU - Yet, Idil

AU - Haller, Toomas

AU - Demirkan, Ayşe

AU - Esko, Tõnu

AU - Zhu, Gu

AU - Böhringer, Stefan

AU - Beekman, Marian

AU - Van Klinken, Jan Bert

AU - Römisch-Margl, Werner

AU - Prehn, Cornelia

AU - Adamski, Jerzy

AU - De Craen, Anton J.M.

AU - Van Leeuwen, Elisabeth M.

AU - Amin, Najaf

AU - Dharuri, Harish

AU - Westra, Harm Jan

AU - Franke, Lude

AU - De Geus, Eco J.C.

AU - Hottenga, Jouke Jan

AU - Willemsen, Gonneke

AU - Henders, Anjali K.

AU - Montgomery, Grant W.

AU - Nyholt, Dale R.

AU - Whitfield, John B.

AU - Penninx, Brenda W.

AU - Spector, Tim D.

AU - Metspalu, Andres

AU - Eline Slagboom, P.

AU - Van Dijk, Ko Willems

AU - 'T Hoen, Peter A.C.

AU - Strauch, Konstantin

AU - Martin, Nicholas G.

AU - Van Ommen, Gert Jan B.

AU - Illig, Thomas

AU - Bell, Jordana T.

AU - Mangino, Massimo

AU - Suhre, Karsten

AU - McCarthy, Mark I.

AU - Gieger, Christian

AU - Isaacs, Aaron

AU - Van Duijn, Cornelia M.

AU - Boomsma, Dorret I.

PY - 2015/6/12

Y1 - 2015/6/12

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 × 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 × 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.

UR - https://www.scopus.com/pages/publications/84935910747

U2 - 10.1038/ncomms8208

DO - 10.1038/ncomms8208

M3 - Article

C2 - 26068415

AN - SCOPUS:84935910747

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 7208

ER -

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

Abstract

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