Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease.

Coronary Artery Disease / genetics Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study Homeostasis Humans Lipidomics Lipids Polymorphism, Single Nucleotide

Journal

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

Informations de publication

Date de publication:
06 06 2022
Historique:
received: 31 08 2021
accepted: 17 05 2022
entrez: 6 6 2022
pubmed: 7 6 2022
medline: 9 6 2022
Statut: epublish

Résumé

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P < 1 × 10

Identifiants

DOI: 10.1038/s41467-022-30875-7 PMID: 35668104 PMC: PMC9170690
pubmed: 35668104
doi: 10.1038/s41467-022-30875-7
pii: 10.1038/s41467-022-30875-7
pmc: PMC9170690
doi:

Substances chimiques

Lipids 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

3124

Subventions

Organisme : NIA NIH HHS
ID : U19 AG063744
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG051550
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : R03 AG054936
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG058942
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG049050
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG061359
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057452
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG046171
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059093
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061788
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA129769
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Gemma Cadby (G)

School of Population and Global Health, University of Western Australia, Crawley, WA, Australia.
ORCID: 0000-0001-7317-6531

Corey Giles (C)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia.
ORCID: 0000-0002-6050-1259

Phillip E Melton (PE)

School of Population and Global Health, University of Western Australia, Crawley, WA, Australia.
Menzies Research Institute, University of Tasmania, Hobart, TAS, Australia.
ORCID: 0000-0003-4026-2964

Kevin Huynh (K)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia.
ORCID: 0000-0001-6170-2207

Natalie A Mellett (NA)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Thy Duong (T)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
ORCID: 0000-0002-2521-078X

Anh Nguyen (A)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Michelle Cinel (M)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Alex Smith (A)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Gavriel Olshansky (G)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia.
ORCID: 0000-0002-5122-5547

Tingting Wang (T)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia.

Marta Brozynska (M)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Mike Inouye (M)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Nina S McCarthy (NS)

School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia.

Amir Ariff (A)

School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.

Joseph Hung (J)

School of Medicine, The University of Western Australia, Crawley, WA, Australia.
Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.
Busselton Population Medical Research Institute Inc., Perth, WA, Australia.
ORCID: 0000-0002-4468-6097

Jennie Hui (J)

Busselton Population Medical Research Institute Inc., Perth, WA, Australia.
PathWest Laboratory Medicine WA, Perth, WA, Australia.

John Beilby (J)

Busselton Population Medical Research Institute Inc., Perth, WA, Australia.
PathWest Laboratory Medicine WA, Perth, WA, Australia.

Marie-Pierre Dubé (MP)

Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Montreal, QC, Canada.

Gerald F Watts (GF)

School of Medicine, The University of Western Australia, Crawley, WA, Australia.
Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, WA, Australia.

Sonia Shah (S)

Institute for Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia.
ORCID: 0000-0001-5860-4526

Naomi R Wray (NR)

Institute for Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia.
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
ORCID: 0000-0001-7421-3357

Wei Ling Florence Lim (WLF)

School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Cooperative research Centre (CRC) for Mental Health, Joondalup, WA, Australia.
ORCID: 0000-0002-8988-2147

Pratishtha Chatterjee (P)

School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
KaRa Institute of Neurological Disease, Sydney, Macquarie Park, NSW, Australia.
ORCID: 0000-0003-4877-1958

Ian Martins (I)

School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
ORCID: 0000-0002-2390-1501

Simon M Laws (SM)

Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.
Collaborative Genomics Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
ORCID: 0000-0002-4355-7082

Tenielle Porter (T)

Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.
Collaborative Genomics Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.

Michael Vacher (M)

Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.
Collaborative Genomics Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
The Australian e-Health Research Centre, Health and Biosecurity, CSIRO, Floreat, WA, Australia.

Ashley I Bush (AI)

The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
ORCID: 0000-0001-8259-9069

Christopher C Rowe (CC)

The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, VIC, Australia.

Victor L Villemagne (VL)

Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, VIC, Australia.
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia.

David Ames (D)

National Ageing Research Institute, Parkville, VIC, Australia.
University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Kew, VIC, Australia.

Colin L Masters (CL)

The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.

Kevin Taddei (K)

School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.

Matthias Arnold (M)

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
ORCID: 0000-0002-4666-0923

Gabi Kastenmüller (G)

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

Kwangsik Nho (K)

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.

Andrew J Saykin (AJ)

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
ORCID: 0000-0002-1376-8532

Xianlin Han (X)

Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
ORCID: 0000-0002-8615-2413

Rima Kaddurah-Daouk (R)

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Duke Institute of Brain Sciences, Duke University, Durham, NC, USA.
Department of Medicine, Duke University, Durham, NC, USA.
ORCID: 0000-0003-1858-5732

Ralph N Martins (RN)

School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Cooperative research Centre (CRC) for Mental Health, Joondalup, WA, Australia.
Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
KaRa Institute of Neurological Disease, Sydney, Macquarie Park, NSW, Australia.

John Blangero (J)

South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, USA.
ORCID: 0000-0001-6250-5723

Peter J Meikle (PJ)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. peter.meikle@baker.edu.au.
Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia. peter.meikle@baker.edu.au.
Monash University, Melbourne, VIC, Australia. peter.meikle@baker.edu.au.
ORCID: 0000-0002-2593-4665

Eric K Moses (EK)

Menzies Research Institute, University of Tasmania, Hobart, TAS, Australia. eric.moses@utas.edu.au.
School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia. eric.moses@utas.edu.au.
ORCID: 0000-0001-7781-4465

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Classifications MeSH

questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Ischémie myocardique › Maladie coronarienne › Maladie des artères coronaires › Comprehensive genetic analysis of the human...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Comprehensive genetic analysis of the human...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Comprehensive genetic analysis of the human...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Comprehensive genetic analysis of the human...
questionsmedicales.fr › Phénomènes physiologiques › Homéostasie › Comprehensive genetic analysis of the human...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Comprehensive genetic analysis of the human...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Métabolomique › Lipidomique › Comprehensive genetic analysis of the human...
questionsmedicales.fr › Lipides › Comprehensive genetic analysis of the human...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Comprehensive genetic analysis of the human...