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

被引：0

作者：

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 Inouye

Nina S. McCarthy

Amir Ariff

Joseph Hung

Jennie Hui

John Beilby

Marie-Pierre Dubé

Gerald F. Watts

Sonia Shah

Naomi R. Wray

Wei Ling Florence Lim

Pratishtha Chatterjee

Ian Martins

Simon M. Laws

Tenielle Porter

Michael Vacher

Ashley I. Bush

Christopher C. Rowe

Victor L. Villemagne

David Ames

Colin L. Masters

Kevin Taddei

Matthias Arnold

Gabi Kastenmüller

Kwangsik Nho

Andrew J. Saykin

Xianlin Han

Rima Kaddurah-Daouk

Ralph N. Martins

John Blangero

Peter J. Meikle

Eric K. Moses

机构：

[1] University of Western Australia,School of Population and Global Health

[2] Baker Heart and Diabetes Institute,Baker Department of Cardiometabolic Health

[3] University of Melbourne,Menzies Research Institute

[4] University of Tasmania,School of Biomedical Sciences

[5] University of Western Australia,School of Women’s and Children’s Health

[6] University of New South Wales,School of Medicine

[7] The University of Western Australia,Department of Cardiovascular Medicine

[8] Sir Charles Gairdner Hospital,Lipid Disorders Clinic, Department of Cardiology

[9] Busselton Population Medical Research Institute Inc.,Institute for Molecular Biosciences

[10] PathWest Laboratory Medicine WA,Queensland Brain Institute

[11] Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre,School of Medical and Health Sciences

[12] Montreal Heart Institute,Department of Biomedical Sciences

[13] Royal Perth Hospital,Centre for Precision Health

[14] University of Queensland,Collaborative Genomics Group, School of Medical and Health Sciences

[15] University of Queensland,Curtin Health Innovation Research Institute

[16] Edith Cowan University,The Florey Department of Neuroscience and Mental Health

[17] Cooperative research Centre (CRC) for Mental Health,Department of Molecular Imaging and Therapy

[18] Macquarie University,Department of Medicine

[19] KaRa Institute of Neurological Disease,Department of Psychiatry and Behavioral Sciences

[20] Edith Cowan University,Department of Radiology and Imaging Sciences

[21] Edith Cowan University,Center for Computational Biology and Bioinformatics

[22] Curtin University,Department of Medical and Molecular Genetics

[23] The Australian e-Health Research Centre,Barshop Institute for Longevity and Aging Studies

[24] Health and Biosecurity,Duke Institute of Brain Sciences

[25] CSIRO,Department of Medicine

[26] The University of Melbourne,South Texas Diabetes and Obesity Institute

[27] Austin Health,undefined

[28] Austin Health,undefined

[29] The University of Melbourne,undefined

[30] National Ageing Research Institute,undefined

[31] University of Melbourne Academic Unit for Psychiatry of Old Age,undefined

[32] St George’s Hospital,undefined

[33] Duke University,undefined

[34] Institute of Computational Biology,undefined

[35] Helmholtz Zentrum München,undefined

[36] German Research Center for Environmental Health,undefined

[37] Indiana University School of Medicine,undefined

[38] Indiana University School of Medicine,undefined

[39] Indiana Alzheimer’s Disease Research Center,undefined

[40] Indiana University School of Medicine,undefined

[41] Indiana University School of Medicine,undefined

[42] University of Texas Health Science Center at San Antonio,undefined

[43] Duke University,undefined

[44] Duke University,undefined

[45] The University of Texas Rio Grande Valley,undefined

[46] Monash University,undefined

来源：

Nature Communications | / 13卷

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摘要：

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 × 10−3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.

引用

共 50 条

[1] Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease
Cadby, Gemma
Giles, Corey
Melton, Phillip E.
Huynh, Kevin
Mellett, Natalie A.
Thy Duong
Anh Nguyen
Cinel, Michelle
Smith, Alex
Olshansky, Gavriel
Wang, Tingting
Brozynska, Marta
Inouye, Mike
McCarthy, Nina S.
Ariff, Amir
Hung, Joseph
Hui, Jennie
Beilby, John
Dube, Marie-Pierre
Watts, Gerald F.
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Wray, Naomi R.
Lim, Wei Ling Florence
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Martins, Ian
Laws, Simon M.
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Bush, Ashley, I
Rowe, Christopher C.
Villemagne, Victor L.
Ames, David
Masters, Colin L.
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Saykin, Andrew J.
Han, Xianlin
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