Rare and common genetic determinants of metabolic individuality and their effects on human health.

Humans Metabolome / genetics Metabolomics Plasma / metabolism Phenotype Metabolism, Inborn Errors / genetics Membrane Proteins / metabolism 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
11 2022
Historique:
received: 10 12 2021
accepted: 16 09 2022
pubmed: 11 11 2022
medline: 22 11 2022
entrez: 10 11 2022
Statut: ppublish

Résumé

Garrod's concept of 'chemical individuality' has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant-metabolite associations (P < 1.25 × 10

Identifiants

DOI: 10.1038/s41591-022-02046-0 PMID: 36357675 PMC: PMC9671801
pubmed: 36357675
doi: 10.1038/s41591-022-02046-0
pii: 10.1038/s41591-022-02046-0
pmc: PMC9671801
doi:

Substances chimiques

SRD5A2 protein, human EC 1.3.99.5
Membrane Proteins 0
3-Oxo-5-alpha-Steroid 4-Dehydrogenase EC 1.3.99.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2321-2332

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC-UU_12015/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : Department of Health
ID : BTRU-2014-10024
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206194
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C864/A14136
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT209492/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L00002/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000143
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 14136
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203810/Z/16/A
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG061359
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L003120/1
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM140287
Pays : United States
Organisme : Medical Research Council
ID : MR/S003746/1
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-20014
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : R01 HG011138
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG063744
Pays : United States
Organisme : British Heart Foundation
ID : RG/18/13/33946
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-20009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N003284/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221651/Z/20/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0401527
Pays : United Kingdom
Organisme : British Heart Foundation
ID : AA/18/6/24223
Pays : United Kingdom
Organisme : British Heart Foundation
ID : BCDSA\100005
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : RF1 AG059093
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057452
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG068026
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_13048
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/13/13/30194
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/12/2/29428
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SP/09/002
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : R35 HG010718
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2022. The Author(s).

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Auteurs

Praveen Surendran (P)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Hinxton, UK.
Rutherford Fund Fellow, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Isobel D Stewart (ID)

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.

Victoria P W Au Yeung (VPW)

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.

Maik Pietzner (M)

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Computational Medicine, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
ORCID: 0000-0003-3437-9963

Johannes Raffler (J)

Institute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Digital Medicine, University Hospital of Augsburg, Augsburg, Germany.

Maria A Wörheide (MA)

Institute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
ORCID: 0000-0002-9326-7227

Chen Li (C)

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.

Rebecca F Smith (RF)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Laura B L Wittemans (LBL)

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Big Data Institute, University of Oxford, Oxford, UK.
Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.

Lorenzo Bomba (L)

Department of Human Genetics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Open Targets, Wellcome Genome Campus, Hinxton, UK.

Cristina Menni (C)

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
ORCID: 0000-0001-9790-0571

Jonas Zierer (J)

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
ORCID: 0000-0002-9693-1859

Niccolò Rossi (N)

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

Patricia A Sheridan (PA)

Metabolon, Morrisville, NC, USA.

Nicholas A Watkins (NA)

NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK.

Massimo Mangino (M)

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK.
ORCID: 0000-0002-2167-7470

Pirro G Hysi (PG)

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

Emanuele Di Angelantonio (E)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Hinxton, UK.
NIHR Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
Health Data Science Research Centre, Human Technopole, Milan, Italy.

Mario Falchi (M)

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
ORCID: 0000-0002-5646-1004

Tim D Spector (TD)

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
ORCID: 0000-0002-9795-0365

Nicole Soranzo (N)

British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Department of Human Genetics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Open Targets, Wellcome Genome Campus, Hinxton, UK.
NIHR Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
Department of Haematology, University of Cambridge, Cambridge, UK.
ORCID: 0000-0003-1095-3852

Gregory A Michelotti (GA)

Metabolon, Morrisville, NC, USA.
ORCID: 0000-0002-3936-4675

Wiebke Arlt (W)

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.
ORCID: 0000-0001-5106-9719

Luca A Lotta (LA)

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.

Spiros Denaxas (S)

Institute of Health Informatics, University College London, London, UK.
Health Data Research UK, London, UK.
British Heart Foundation Data Science Centre, London, UK.

Harry Hemingway (H)

Institute of Health Informatics, University College London, London, UK.
Health Data Research UK, London, UK.

Eric R Gamazon (ER)

Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Clare Hall & MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.

Joanna M M Howson (JMM)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, UK.
ORCID: 0000-0001-7618-0050

Angela M Wood (AM)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Hinxton, UK.
NIHR Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
MRC Biostatistics Unit, Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK.
The Alan Turing Institute, London, UK.

John Danesh (J)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Hinxton, UK.
Department of Human Genetics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
NIHR Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.

Nicholas J Wareham (NJ)

Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Hinxton, UK.
MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
ORCID: 0000-0003-1422-2993

Gabi Kastenmüller (G)

Institute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
ORCID: 0000-0002-2368-7322

Eric B Fauman (EB)

Internal Medicine Research Unit, Pfizer Worldwide Research, Development and Medical, Cambridge, MA, USA.
ORCID: 0000-0002-9739-0249

Karsten Suhre (K)

Department of Biophysics and Physiology, Weill Cornell Medicine-Qatar, Doha, Qatar.

Adam S Butterworth (AS)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. asb38@medschl.cam.ac.uk.
British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. asb38@medschl.cam.ac.uk.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Hinxton, UK. asb38@medschl.cam.ac.uk.
NIHR Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK. asb38@medschl.cam.ac.uk.
ORCID: 0000-0002-6915-9015

Claudia Langenberg (C)

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. Claudia.Langenberg@mrc-epid.cam.ac.uk.
Computational Medicine, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany. Claudia.Langenberg@mrc-epid.cam.ac.uk.
Precision Healthcare University Research Institute, Queen Mary University of London, London, UK. Claudia.Langenberg@mrc-epid.cam.ac.uk.
ORCID: 0000-0002-5017-7344

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Rare and common genetic determinants of...
questionsmedicales.fr › Métabolisme › Métabolome › Rare and common genetic determinants of...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Métabolomique › Rare and common genetic determinants of...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Sang › Plasma sanguin › Rare and common genetic determinants of...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Rare and common genetic determinants of...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Erreurs innées du métabolisme › Rare and common genetic determinants of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Rare and common genetic determinants of...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Oxidoreductases acting on CH-CH group donors › 3-Oxo-5-alpha-Steroid 4-Dehydrogenase › Rare and common genetic determinants of...