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

Author

Listed:
  • Gemma Cadby

    (University of Western Australia)

  • Corey Giles

    (Baker Heart and Diabetes Institute
    University of Melbourne)

  • Phillip E. Melton

    (University of Western Australia
    University of Tasmania)

  • Kevin Huynh

    (Baker Heart and Diabetes Institute
    University of Melbourne)

  • Natalie A. Mellett

    (Baker Heart and Diabetes Institute)

  • Thy Duong

    (Baker Heart and Diabetes Institute)

  • Anh Nguyen

    (Baker Heart and Diabetes Institute)

  • Michelle Cinel

    (Baker Heart and Diabetes Institute)

  • Alex Smith

    (Baker Heart and Diabetes Institute)

  • Gavriel Olshansky

    (Baker Heart and Diabetes Institute
    University of Melbourne)

  • Tingting Wang

    (Baker Heart and Diabetes Institute
    University of Melbourne)

  • Marta Brozynska

    (Baker Heart and Diabetes Institute)

  • Mike Inouye

    (Baker Heart and Diabetes Institute)

  • Nina S. McCarthy

    (University of Western Australia)

  • Amir Ariff

    (University of New South Wales)

  • Joseph Hung

    (The University of Western Australia
    Sir Charles Gairdner Hospital
    Busselton Population Medical Research Institute Inc.)

  • Jennie Hui

    (Busselton Population Medical Research Institute Inc.
    PathWest Laboratory Medicine WA)

  • John Beilby

    (Busselton Population Medical Research Institute Inc.
    PathWest Laboratory Medicine WA)

  • Marie-Pierre Dubé

    (Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute)

  • Gerald F. Watts

    (The University of Western Australia
    Royal Perth Hospital)

  • Sonia Shah

    (University of Queensland)

  • Naomi R. Wray

    (University of Queensland
    University of Queensland)

  • Wei Ling Florence Lim

    (Edith Cowan University
    Cooperative research Centre (CRC) for Mental Health)

  • Pratishtha Chatterjee

    (Edith Cowan University
    Macquarie University
    KaRa Institute of Neurological Disease)

  • Ian Martins

    (Edith Cowan University)

  • Simon M. Laws

    (Edith Cowan University
    Edith Cowan University
    Curtin University)

  • Tenielle Porter

    (Edith Cowan University
    Edith Cowan University
    Curtin University)

  • Michael Vacher

    (Edith Cowan University
    Edith Cowan University
    The Australian e-Health Research Centre, Health and Biosecurity, CSIRO)

  • Ashley I. Bush

    (The University of Melbourne)

  • Christopher C. Rowe

    (The University of Melbourne
    Austin Health)

  • Victor L. Villemagne

    (Austin Health
    Austin Health, The University of Melbourne)

  • David Ames

    (National Ageing Research Institute
    University of Melbourne Academic Unit for Psychiatry of Old Age, St George’s Hospital)

  • Colin L. Masters

    (The University of Melbourne)

  • Kevin Taddei

    (Edith Cowan University)

  • Matthias Arnold

    (Duke University
    Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Gabi Kastenmüller

    (Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Kwangsik Nho

    (Indiana University School of Medicine
    Indiana University School of Medicine
    Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine)

  • Andrew J. Saykin

    (Indiana University School of Medicine
    Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine
    Indiana University School of Medicine)

  • Xianlin Han

    (University of Texas Health Science Center at San Antonio)

  • Rima Kaddurah-Daouk

    (Duke University
    Duke University
    Duke University)

  • Ralph N. Martins

    (Edith Cowan University
    Cooperative research Centre (CRC) for Mental Health
    Macquarie University
    KaRa Institute of Neurological Disease)

  • John Blangero

    (The University of Texas Rio Grande Valley)

  • Peter J. Meikle

    (Baker Heart and Diabetes Institute
    University of Melbourne
    Monash University)

  • Eric K. Moses

    (University of Tasmania
    University of Western Australia)

Abstract

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

Suggested Citation

  • Gemma Cadby & Corey Giles & Phillip E. Melton & Kevin Huynh & Natalie A. Mellett & Thy Duong & Anh Nguyen & Michelle Cinel & Alex Smith & Gavriel Olshansky & Tingting Wang & Marta Brozynska & Mike Ino, 2022. "Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30875-7
    DOI: 10.1038/s41467-022-30875-7
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    References listed on IDEAS

    as
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    1. Kenneth A. Wilson & Sudipta Bar & Eric B. Dammer & Enrique M. Carrera & Brian A. Hodge & Tyler A. U. Hilsabeck & Joanna Bons & George W. Brownridge & Jennifer N. Beck & Jacob Rose & Melia Granath-Pane, 2024. "OXR1 maintains the retromer to delay brain aging under dietary restriction," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Aleksandar Dakic & Jingqin Wu & Tingting Wang & Kevin Huynh & Natalie Mellett & Thy Duong & Habtamu B. Beyene & Dianna J. Magliano & Jonathan E. Shaw & Melinda J. Carrington & Michael Inouye & Jean Y., 2024. "Imputation of plasma lipid species to facilitate integration of lipidomic datasets," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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