title: An atlas of genetic influences on human blood metabolites.
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.
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Pfizer Worldwide Research and Development, Computational Sciences Center of Emphasis, 200 Cambridgepark Drive, Cambridge MA, 02140, USA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Fauman
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Petersen
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Krumsiek
authors.affiliation: European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, CB10 1SD, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Santos
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Arnold
authors.affiliation: Department of Twin research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK.
authors.forename: Idil
authors.initials: I
authors.lastname: Erte
authors.affiliation: Department of Human Genetics, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal H3A 1A5, Canada.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Forgetta
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.
authors.forename: Tsun-Po
authors.initials: TP
authors.lastname: Yang
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Walter
authors.affiliation: Department of Twin research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.|Department of Hematology, University of Cambridge, Long Road, Cambridge CB2 2PT, UK.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.
authors.forename: Louella
authors.initials: L
authors.lastname: Vasquez
authors.affiliation: Department of Twin research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK.|School of Medicine, University of Nottingham, Nottingham NG5 1PB, UK.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.affiliation: Pfizer Worldwide Research and Development, Clinical Research Statistics, 558 Eastern Point Rd, Groton CT 06340, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Hyde
authors.affiliation: Pfizer Worldwide Research and Development, Computational Sciences Center of Emphasis, 200 Cambridgepark Drive, Cambridge MA, 02140, USA.
authors.forename: Vicky
authors.initials: V
authors.lastname: Wang
authors.affiliation: Pfizer Worldwide Research and Development, Computational Sciences Center of Emphasis, 200 Cambridgepark Drive, Cambridge MA, 02140, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ziemek
authors.affiliation: Pfizer Worldwide Research and Development, Computational Sciences Center of Emphasis, 200 Cambridgepark Drive, Cambridge MA, 02140, USA.
authors.forename: Phoebe
authors.initials: P
authors.lastname: Roberts
authors.affiliation: Pfizer Worldwide Research and Development, Computational Sciences Center of Emphasis, 200 Cambridgepark Drive, Cambridge MA, 02140, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xi
authors.affiliation: Department of Human Genetics, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal H3A 1A5, Canada.|Genome Quebec Innovation Centre, McGill University, Montreal QCH3A 1A5, Canada.
authors.forename: Elin
authors.initials: E
authors.lastname: Grundberg
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.affiliation: Department of Human Genetics, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal H3A 1A5, Canada.|Department of Medicine, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal H3A 1A5, Canada.
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
authors.affiliation: Metabolon Inc., 617 Davis Drive, Durham, NC 27713, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mohney
authors.affiliation: Metabolon Inc., 617 Davis Drive, Durham, NC 27713, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Milburn
authors.affiliation: Pfizer Worldwide Research and Development, Cardiovascular and Metabolic Diseases, 620 Memorial Drive, Cambridge, MA 02139, USA.
authors.forename: Sally L
authors.initials: SL
authors.lastname: John
authors.affiliation: Pfizer Worldwide Research and Development, Cardiovascular and Metabolic Diseases, 620 Memorial Drive, Cambridge, MA 02139, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Trimmer
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.|Department of Mathematics, Technische Universität München, Garching, Germany.
authors.forename: Fabian J
authors.initials: FJ
authors.lastname: Theis
authors.affiliation: European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, CB10 1SD, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Overington
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.|Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: Pfizer Worldwide Research and Development, Clinical Research Statistics, 558 Eastern Point Rd, Groton CT 06340, USA.
authors.forename: M Julia
authors.initials: MJ
authors.lastname: Brosnan
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: Department of Twin research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.|Department of Hematology, Long Road, Cambridge CB2 0PT, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001769:Blood / Q000378:metabolism*; D001774:Blood Chemical Analysis; D015331:Cohort Studies; D019295:Computational Biology; D057225:Data Mining; D005060:Europe; D005260:Female; D020869:Gene Expression Profiling; D056426:Genetic Loci / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D020407:Internet; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics; D055432:Metabolomics; D008875:Middle Aged; D006113:United Kingdom; D055815:Young Adult