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Nat Genet. 2014 Jun;46(6):543-550. doi: 10.1038/ng.2982. Epub 2014 May 11.

An atlas of genetic influences on human blood metabolites.

Author information

1
Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.
2
Pfizer Worldwide Research and Development, Computational Sciences Center of Emphasis, 200 Cambridgepark Drive, Cambridge MA, 02140, USA.
3
Institute of Genetic Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
4
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
5
European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, CB10 1SD, UK.
6
Department of Twin research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK.
7
Department of Human Genetics, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal H3A 1A5, Canada.
8
Department of Hematology, University of Cambridge, Long Road, Cambridge CB2 2PT, UK.
9
School of Medicine, University of Nottingham, Nottingham NG5 1PB, UK.
10
Pfizer Worldwide Research and Development, Clinical Research Statistics, 558 Eastern Point Rd, Groton CT 06340, USA.
11
Genome Quebec Innovation Centre, McGill University, Montreal QCH3A 1A5, Canada.
12
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
13
Department of Medicine, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal H3A 1A5, Canada.
14
Metabolon Inc., 617 Davis Drive, Durham, NC 27713, USA.
15
Pfizer Worldwide Research and Development, Cardiovascular and Metabolic Diseases, 620 Memorial Drive, Cambridge, MA 02139, USA.
16
Department of Mathematics, Technische Universität München, Garching, Germany.
17
Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.
18
Department of Hematology, Long Road, Cambridge CB2 0PT, UK.
#
Contributed equally

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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