Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
26068415
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 × 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.
DATE PUBLISHED
2015
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/08/15
accepted 2015/04/20
entrez 2015/06/13 06:00
pubmed 2015/06/13 06:00
medline 2016/03/24 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Draisma HH Draisma Harmen H M HH 1] Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, Amsterdam 1081 BT, The Netherlands [2] The EMGO+ Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands [3] Neuroscience Campus Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
Pool R Pool René R 1] Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, Amsterdam 1081 BT, The Netherlands [2] The EMGO+ Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands [3] BBMRI-NL: Infrastructure for the Application of Metabolomics Technology in Epidemiology (RP4), S4-P, Postbus 9600, Leiden 2300 RC, The Netherlands.
Kobl M Kobl Michael M Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.
Jansen R Jansen Rick R Department of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, VUmc, A.J. Ernststraat 1187, Amsterdam 1081 HL, The Netherlands.
Petersen AK Petersen Ann-Kristin AK Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.
Vaarhorst AA Vaarhorst Anika A M AA 1] BBMRI-NL: Infrastructure for the Application of Metabolomics Technology in Epidemiology (RP4), S4-P, Postbus 9600, Leiden 2300 RC, The Netherlands [2] Department of Molecular Epidemiology, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands [3] Netherlands Consortium for Healthy Aging, Leiden University Medical Center, Leiden, The Netherlands.
Yet I Yet Idil I Department of Twin Research and Genetic Epidemiology, King's College London, Westminster Bridge Road, London SE1 7EH, UK.
Haller T Haller Toomas T Estonian Genome Center, University of Tartu, 23b Riia Street, Tartu 51010, Estonia.
Demirkan A Demirkan Ayşe A 1] Department of Human Genetics, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands [2] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, P.O. Box 2040, Rotterdam 3000 CA, The Netherlands.
Esko T Esko Tõnu T 1] Estonian Genome Center, University of Tartu, 23b Riia Street, Tartu 51010, Estonia [2] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, 300 Longwood Ave, Boston MA02115, Massachusetts, USA [3] Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 2142, USA [4] Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 0330, Boston MA 02115, Massachusetts, USA.
Zhu G Zhu Gu G Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia.
Böhringer S Böhringer Stefan S Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands.
Beekman M Beekman Marian M Department of Molecular Epidemiology, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands.
van Klinken JB van Klinken Jan Bert JB Department of Human Genetics, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands.
Römisch-Margl W Römisch-Margl Werner W Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.
Prehn C Prehn Cornelia C Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Ingolstädter Landstraße1, Neuherberg 85764, Germany.
Adamski J Adamski Jerzy J 1] Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Ingolstädter Landstraße1, Neuherberg 85764, Germany [2] German Center for Diabetes Research at Helmholtz Zentrum München, Ingolstädter Landstr. 1, Neuherberg 85764, Germany [3] Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan 85350, Germany.
de Craen AJ de Craen Anton J M AJ Department of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands.
van Leeuwen EM van Leeuwen Elisabeth M EM Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, P.O. Box 2040, Rotterdam 3000 CA, The Netherlands.
Amin N Amin Najaf N Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, P.O. Box 2040, Rotterdam 3000 CA, The Netherlands.
Dharuri H Dharuri Harish H Department of Human Genetics, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands.
Westra HJ Westra Harm-Jan HJ Department of Genetics, CB50, University Medical Center Groningen, University of Groningen, P.O. Box 30001, Groningen 9700 RB, The Netherlands.
Franke L Franke Lude L Department of Genetics, CB50, University Medical Center Groningen, University of Groningen, P.O. Box 30001, Groningen 9700 RB, The Netherlands.
de Geus EJ de Geus Eco J C EJ 1] Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, Amsterdam 1081 BT, The Netherlands [2] The EMGO+ Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
Hottenga JJ Hottenga Jouke Jan JJ 1] Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, Amsterdam 1081 BT, The Netherlands [2] The EMGO+ Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
Willemsen G Willemsen Gonneke G 1] Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, Amsterdam 1081 BT, The Netherlands [2] The EMGO+ Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
Henders AK Henders Anjali K AK Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia.
Montgomery GW Montgomery Grant W GW Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia.
Nyholt DR Nyholt Dale R DR 1] Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia [2] Statistical and Genomic Epidemiology, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove QLD 4059, Queensland, Australia.
Whitfield JB Whitfield John B JB Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia.
Penninx BW Penninx Brenda W BW 1] The EMGO+ Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands [2] Department of Psychiatry, VU University Medical Center, A.J. Ernststraat 1187, Amsterdam 1081 HL, The Netherlands.
Spector TD Spector Tim D TD Department of Twin Research and Genetic Epidemiology, King's College London, Westminster Bridge Road, London SE1 7EH, UK.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, 23b Riia Street, Tartu 51010, Estonia.
Eline Slagboom P Eline Slagboom P P 1] BBMRI-NL: Infrastructure for the Application of Metabolomics Technology in Epidemiology (RP4), S4-P, Postbus 9600, Leiden 2300 RC, The Netherlands [2] Department of Molecular Epidemiology, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands.
van Dijk KW van Dijk Ko Willems KW 1] Department of Human Genetics, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands [2] Department of Endocrinology, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands.
't Hoen PA 't Hoen Peter A C PA Department of Human Genetics, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands.
Strauch K Strauch Konstantin K 1] Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg 85764, Germany [2] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich 81377, Germany.
Martin NG Martin Nicholas G NG Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia.
van Ommen GJ van Ommen Gert-Jan B GJ Department of Human Genetics, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands.
Illig T Illig Thomas T 1] Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany [2] Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany [3] Institute for Human Genetics, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
Bell JT Bell Jordana T JT Department of Twin Research and Genetic Epidemiology, King's College London, Westminster Bridge Road, London SE1 7EH, UK.
Mangino M Mangino Massimo M Department of Twin Research and Genetic Epidemiology, King's College London, Westminster Bridge Road, London SE1 7EH, UK.
Suhre K Suhre Karsten K 1] Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany [2] Faculty of Biology, Ludwig-Maximilians-Universität, Planegg-Martinsried 82152, Germany [3] Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar (WCMC-Q), PO Box 24144, Education City-Qatar Foundation, Doha, Qatar.
McCarthy MI McCarthy Mark I MI 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington OX3 7LE, UK [3] Oxford National Institute for Health Research Biomedical Research Centre, The Joint Research Office, Block 60, Churchill Hospital, Old Road, Headington OX3 7LE, UK.
Gieger C Gieger Christian C 1] Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg 85764, Germany [2] Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany [3] Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.
Isaacs A Isaacs Aaron A Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, P.O. Box 2040, Rotterdam 3000 CA, The Netherlands.
van Duijn CM van Duijn Cornelia M CM 1] BBMRI-NL: Infrastructure for the Application of Metabolomics Technology in Epidemiology (RP4), S4-P, Postbus 9600, Leiden 2300 RC, The Netherlands [2] Netherlands Consortium for Healthy Aging, Leiden University Medical Center, Leiden, The Netherlands [3] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, P.O. Box 2040, Rotterdam 3000 CA, The Netherlands.
Boomsma DI Boomsma Dorret I DI 1] Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, Amsterdam 1081 BT, The Netherlands [2] The EMGO+ Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands [3] BBMRI-NL: Infrastructure for the Application of Metabolomics Technology in Epidemiology (RP4), S4-P, Postbus 9600, Leiden 2300 RC, The Netherlands.
INVESTIGATORS
JOURNAL
VOLUME: 6
ISSUE:
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2015
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
230374 European Research Council International
R01DK075787 NIDDK NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Blood metabolism
Genome-Wide Association Study metabolism
Humans metabolism
Polymorphism, Single Nucleotide metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
EMS66678 NLM
PMC4745136 NLM