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PMID |
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TITLE |
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Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels. |
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ABSTRACT |
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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. |
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DATE PUBLISHED |
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HISTORY |
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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 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Draisma HH |
|
Draisma |
Harmen H M |
HH |
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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 |
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Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg 85764, Germany. |
Jansen R |
|
Jansen |
Rick |
R |
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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 |
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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 |
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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 |
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Department of Twin Research and Genetic Epidemiology, King's College London, Westminster Bridge Road, London SE1 7EH, UK. |
Haller T |
|
Haller |
Toomas |
T |
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Estonian Genome Center, University of Tartu, 23b Riia Street, Tartu 51010, Estonia. |
Demirkan A |
|
Demirkan |
Ayşe |
A |
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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 |
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Esko |
Tõnu |
T |
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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 |
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Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia. |
Böhringer S |
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Böhringer |
Stefan |
S |
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Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands. |
Beekman M |
|
Beekman |
Marian |
M |
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Department of Molecular Epidemiology, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands. |
van Klinken JB |
|
van Klinken |
Jan Bert |
JB |
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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 |
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Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany. |
Prehn C |
|
Prehn |
Cornelia |
C |
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Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Ingolstädter Landstraße1, Neuherberg 85764, Germany. |
Adamski J |
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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 |
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de Craen |
Anton J M |
AJ |
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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 |
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Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, P.O. Box 2040, Rotterdam 3000 CA, The Netherlands. |
Amin N |
|
Amin |
Najaf |
N |
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Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, P.O. Box 2040, Rotterdam 3000 CA, The Netherlands. |
Dharuri H |
|
Dharuri |
Harish |
H |
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Department of Human Genetics, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands. |
Westra HJ |
|
Westra |
Harm-Jan |
HJ |
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Department of Genetics, CB50, University Medical Center Groningen, University of Groningen, P.O. Box 30001, Groningen 9700 RB, The Netherlands. |
Franke L |
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Franke |
Lude |
L |
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Department of Genetics, CB50, University Medical Center Groningen, University of Groningen, P.O. Box 30001, Groningen 9700 RB, The Netherlands. |
de Geus EJ |
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de Geus |
Eco J C |
EJ |
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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 |
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Hottenga |
Jouke Jan |
JJ |
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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 |
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Willemsen |
Gonneke |
G |
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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 |
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Henders |
Anjali K |
AK |
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Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia. |
Montgomery GW |
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Montgomery |
Grant W |
GW |
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Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia. |
Nyholt DR |
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Nyholt |
Dale R |
DR |
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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 |
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Whitfield |
John B |
JB |
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Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia. |
Penninx BW |
|
Penninx |
Brenda W |
BW |
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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 |
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Spector |
Tim D |
TD |
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Department of Twin Research and Genetic Epidemiology, King's College London, Westminster Bridge Road, London SE1 7EH, UK. |
Metspalu A |
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Metspalu |
Andres |
A |
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Estonian Genome Center, University of Tartu, 23b Riia Street, Tartu 51010, Estonia. |
Eline Slagboom P |
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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 |
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Department of Human Genetics, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands. |
Strauch K |
|
Strauch |
Konstantin |
K |
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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 |
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Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane 4006, Australia. |
van Ommen GJ |
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van Ommen |
Gert-Jan B |
GJ |
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Department of Human Genetics, Leiden University Medical Center, S4-P, PO Box 9600, Leiden 2300 RC, The Netherlands. |
Illig T |
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Illig |
Thomas |
T |
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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 |
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Bell |
Jordana T |
JT |
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Department of Twin Research and Genetic Epidemiology, King's College London, Westminster Bridge Road, London SE1 7EH, UK. |
Mangino M |
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Mangino |
Massimo |
M |
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Department of Twin Research and Genetic Epidemiology, King's College London, Westminster Bridge Road, London SE1 7EH, UK. |
Suhre K |
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Suhre |
Karsten |
K |
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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 |
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McCarthy |
Mark I |
MI |
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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 |
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Gieger |
Christian |
C |
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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 |
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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 |
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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 |
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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. |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 6 |
ISSUE: |
TITLE: Nature communications |
ISOABBREVIATION: Nat Commun |
YEAR: 2015 |
MONTH: |
DAY: |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 2041-1723 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Nat Commun |
COUNTRY: England |
ISSNLINKING: 2041-1723 |
NLMUNIQUEID: 101528555 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Meta-Analysis |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
Cites |
Nat Genet. 2010 Feb;42(2):137-41 |
20037589 |
|
Cites |
PLoS Genet. 2009 Oct;5(10):e1000672 |
19798445 |
|
Cites |
Br J Cancer. 2010 Mar 16;102(6):1003-9 |
20179710 |
|
Cites |
J Lipid Res. 2010 Jul;51(7):1793-800 |
20176858 |
|
Cites |
BMC Bioinformatics. 2010;11:288 |
20509871 |
|
Cites |
Bioinformatics. 2010 Sep 1;26(17):2190-1 |
20616382 |
|
Cites |
Bioinformatics. 2010 Sep 15;26(18):2336-7 |
20634204 |
|
Cites |
Nucleic Acids Res. 2011 Jan;39(Database issue):D712-7 |
21071422 |
|
Cites |
Am J Hum Genet. 2011 Jan 7;88(1):76-82 |
21167468 |
|
Cites |
Nat Genet. 2011 Apr;43(4):333-8 |
21378990 |
|
Cites |
Database (Oxford). 2011;2011:bar009 |
21447597 |
|
Cites |
Mol Psychiatry. 2011 Jul;16(7):773-83 |
20567237 |
|
Cites |
PLoS Genet. 2011 Aug;7(8):e1002215 |
21852955 |
|
Cites |
Nature. 2011 Sep 1;477(7362):54-60 |
21886157 |
|
Cites |
PLoS Genet. 2011 Sep;7(9):e1002270 |
21931564 |
|
Cites |
Hum Mol Genet. 2011 Oct 15;20(R2):R198-205 |
21875899 |
|
Cites |
Hum Mutat. 2012 Jan;33(1):189-97 |
21990100 |
|
Cites |
Hum Mol Genet. 2012 Mar 15;21(6):1444-55 |
22156771 |
|
Cites |
PLoS Genet. 2012;8(2):e1002490 |
22359512 |
|
Cites |
Nat Genet. 2012 Mar;44(3):269-76 |
22286219 |
|
Cites |
Am J Kidney Dis. 2012 Aug;60(2):197-206 |
22464876 |
|
Cites |
Diabet Med. 2012 Oct;29(10):e365-8 |
22803961 |
|
Cites |
Nat Rev Genet. 2012 Nov;13(11):759-69 |
23032255 |
|
Cites |
Nat Genet. 2013 Jan;45(1):25-33 |
23202125 |
|
Cites |
Nat Genet. 2013 May;45(5):501-12 |
23563607 |
|
Cites |
Cell Metab. 2013 Jul 2;18(1):130-43 |
23823483 |
|
Cites |
Twin Res Hum Genet. 2013 Oct;16(5):948-61 |
23985338 |
|
Cites |
PLoS Genet. 2014 Mar;10(3):e1004212 |
24625756 |
|
Cites |
Heredity (Edinb). 2005 Sep;95(3):221-7 |
16077740 |
|
Cites |
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D181-6 |
16381841 |
|
Cites |
Eur J Clin Nutr. 2006 Dec;60(12):1406-13 |
16788709 |
|
Cites |
Am J Hum Genet. 2007 Sep;81(3):559-75 |
17701901 |
|
Cites |
Nature. 2007 Oct 18;449(7164):851-61 |
17943122 |
|
Cites |
Genet Epidemiol. 2008 May;32(4):381-5 |
18348202 |
|
Cites |
PLoS Genet. 2008 Nov;4(11):e1000282 |
19043545 |
|
Cites |
J Am Coll Cardiol. 2009 Jun 2;53(22):2061-7 |
19477356 |
|
Cites |
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7 |
19474294 |
|
Cites |
Nature. 2009 Aug 6;460(7256):748-52 |
19571811 |
|
Cites |
Nat Genet. 2014 Jun;46(6):543-50 |
24816252 |
|
Cites |
Mol Psychiatry. 2015 May;20(5):647-56 |
25288136 |
|
Cites |
Nucleic Acids Res. 2000 Jan 1;28(1):27-30 |
10592173 |
|
Cites |
Nat Genet. 2000 May;25(1):25-9 |
10802651 |
|
Cites |
Nucleic Acids Res. 2003 Jul 1;31(13):3784-8 |
12824418 |
|
Cites |
Genome Res. 2003 Nov;13(11):2498-504 |
14597658 |
|
Cites |
J Biol Chem. 2010 Feb 26;285(9):6275-84 |
20037140 |
|
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
230374 |
European Research Council |
International |
R01DK075787 |
NIDDK NIH HHS |
United States |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Blood |
metabolism |
Genome-Wide Association Study |
metabolism |
Humans |
metabolism |
Polymorphism, Single Nucleotide |
metabolism |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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OTHERID |
SOURCE |
EMS66678 |
NLM |
PMC4745136 |
NLM |
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