Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke.

Atrial Fibrillation / genetics Blood Proteins / genetics Diabetes Mellitus, Type 2 / genetics Genetic Predisposition to Disease Genome-Wide Association Study Humans Mendelian Randomization Analysis Polymorphism, Single Nucleotide Proteome / genetics Risk Factors Stroke / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
17 10 2022
Historique:
received: 16 10 2021
accepted: 28 09 2022
entrez: 17 10 2022
pubmed: 18 10 2022
medline: 20 10 2022
Statut: epublish

Résumé

Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P ≤ 1.62 × 10

Identifiants

DOI: 10.1038/s41467-022-33675-1 PMID: 36253349 PMC: PMC9576777
pubmed: 36253349
doi: 10.1038/s41467-022-33675-1
pii: 10.1038/s41467-022-33675-1
pmc: PMC9576777
doi:

Substances chimiques

Blood Proteins 0
Proteome 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6143

Subventions

Organisme : Medical Research Council
ID : MR/L003120/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S003746/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/16/4/32218
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Lingyan Chen (L)

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: 0000-0003-3750-6761

James E Peters (JE)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Department of Immunology and Inflammation, Faculty of Medicine, Imperial College London, London, UK.
ORCID: 0000-0002-9415-3440

Bram Prins (B)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
ORCID: 0000-0001-5774-034X

Elodie Persyn (E)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Department of Medical and Molecular Genetics, King's College London, London, UK.
Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
ORCID: 0000-0001-9104-1972

Matthew Traylor (M)

Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, UK.
Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.

Praveen Surendran (P)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Rutherford Fund Fellow, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, Cambridge, UK.

Savita Karthikeyan (S)

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

Ekaterina Yonova-Doing (E)

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.

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, University of Cambridge, Cambridge, UK.
National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
Health Data Science Research Centre, Human Technopole, Milan, Italy.

David J Roberts (DJ)

National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.
NHS Blood and Transplant-Oxford Centre, Level 2, John Radcliffe Hospital, Oxford, UK.
Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Nicholas A Watkins (NA)

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

Willem H Ouwehand (WH)

British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.
NHS Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge, UK.
Department of Haematology, University of Cambridge, Cambridge, UK.
Wellcome Sanger Institute, Hinxton, UK.
ORCID: 0000-0002-7744-1790

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, University of Cambridge, Cambridge, UK.
National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
Department of Human Genetics, Wellcome Sanger Institute, Hinxton, UK.

Cathryn M Lewis (CM)

Department of Medical and Molecular Genetics, King's College London, London, UK.
Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.
ORCID: 0000-0002-8249-8476

Paola G Bronson (PG)

R&D Translational Biology, Biogen, Inc., Cambridge, MA, USA.
ORCID: 0000-0001-9996-9812

Hugh S Markus (HS)

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Stephen Burgess (S)

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, University of Cambridge, Cambridge, UK.
Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK.
ORCID: 0000-0001-5365-8760

Adam S Butterworth (AS)

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, University of Cambridge, Cambridge, UK.
National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
ORCID: 0000-0002-6915-9015

Joanna M M Howson (JMM)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. jmmh2@medschl.cam.ac.uk.
Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, UK. jmmh2@medschl.cam.ac.uk.
ORCID: 0000-0001-7618-0050

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Classifications MeSH

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questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › Systematic Mendelian randomization using the...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Systematic Mendelian randomization using the...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Systematic Mendelian randomization using the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Systematic Mendelian randomization using the...
questionsmedicales.fr › Techniques d'investigation › Analyse de randomisation mendélienne › Systematic Mendelian randomization using the...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Systematic Mendelian randomization using the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéome › Systematic Mendelian randomization using the...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Systematic Mendelian randomization using the...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Angiopathies intracrâniennes › Accident vasculaire cérébral › Systematic Mendelian randomization using the...