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Nat Genet. 2014 Jun;46(6):543-50. doi: 10.1038/ng.2982. Epub 2014 May 11.

An atlas of genetic influences on human blood metabolites.

Author information

1
1] Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. [2] [3].
2
1] Computational Sciences Center of Emphasis, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA. [2].
3
1] Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany. [2].
4
1] Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany. [2].
5
European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Hinxton, UK.
6
Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
7
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
8
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
9
Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
10
1] Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. [2] Department of Hematology, University of Cambridge, Cambridge, UK.
11
1] Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. [2] School of Medicine, University of Nottingham, Nottingham, UK.
12
Clinical Research Statistics, Pfizer Worldwide Research and Development, Groton, Connecticut, USA.
13
Computational Sciences Center of Emphasis, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA.
14
1] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [2] McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
15
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
16
1] Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. [2] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [3] Department of Medicine, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal, Quebec, Canada.
17
Metabolon, Inc., Durham, North Carolina, USA.
18
Biotherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA.
19
1] Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA. [2].
20
1] Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany. [2] Department of Mathematics, Technische Universität München, Garching, Germany.
21
1] Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany. [2] Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation, Doha, Qatar. [3].
22
1] Clinical Research Statistics, Pfizer Worldwide Research and Development, Groton, Connecticut, USA. [2].
23
1] Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany. [2].
24
1] Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. [2].
25
1] Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. [2] Department of Hematology, University of Cambridge, Cambridge, UK. [3].

Abstract

Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most comprehensive exploration of genetic loci influencing human metabolism thus far, comprising 7,824 adult individuals from 2 European population studies. We report genome-wide significant associations at 145 metabolic loci and their biochemical connectivity with more than 400 metabolites in human blood. We extensively characterize the resulting in vivo blueprint of metabolism in human blood by integrating it with information on gene expression, heritability and overlap with known loci for complex disorders, inborn errors of metabolism and pharmacological targets. We further developed a database and web-based resources for data mining and results visualization. Our findings provide new insights into the role of inherited variation in blood metabolic diversity and identify potential new opportunities for drug development and for understanding disease.

PMID:
24816252
PMCID:
PMC4064254
DOI:
10.1038/ng.2982
[Indexed for MEDLINE]
Free PMC Article
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