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.; Duong, Thy; Nguyen, Anh; Cinel, Michelle; Smith, Alex; Olshansky, Gavriel; Wang, Tingting; Brozynska, Marta; Inouye, Mike; McCarthy, Nina S.; Ariff, Amir; Hung, Joseph; Hui, Jennie; Beilby, John; Dubé, Marie-Pierre; Watts, Gerald F.; Shah, Sonia; Wray, Naomi R.; Lim, Wei Ling Florence; Chatterjee, Pratishtha; Martins, Ian; Laws, Simon M.; Porter, Tenielle; Vacher, Michael; Bush, Ashley I.; Rowe, Christopher C.; Villemagne, Victor L.; Ames, David; Masters, Colin L.; Taddei, Kevin; Arnold, Matthias; Kastenmüller, Gabi; Nho, Kwangsik; Saykin, Andrew J.; Han, Xianlin; Kaddurah-Daouk, Rima; Martins, Ralph N.; Blangero, John; Meikle, Peter J.; Moses, Eric K.

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

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 () and Eric K. Moses ()
Additional contact information
Gemma Cadby: University of Western Australia
Corey Giles: Baker Heart and Diabetes Institute
Phillip E. Melton: University of Western Australia
Kevin Huynh: Baker Heart and Diabetes Institute
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
Tingting Wang: Baker Heart and Diabetes Institute
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
Jennie Hui: Busselton Population Medical Research Institute Inc.
John Beilby: Busselton Population Medical Research Institute Inc.
Marie-Pierre Dubé: Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute
Gerald F. Watts: The University of Western Australia
Sonia Shah: University of Queensland
Naomi R. Wray: University of Queensland
Wei Ling Florence Lim: Edith Cowan University
Pratishtha Chatterjee: Edith Cowan University
Ian Martins: Edith Cowan University
Simon M. Laws: Edith Cowan University
Tenielle Porter: Edith Cowan University
Michael Vacher: Edith Cowan University
Ashley I. Bush: The University of Melbourne
Christopher C. Rowe: The University of Melbourne
Victor L. Villemagne: Austin Health
David Ames: National Ageing Research Institute
Colin L. Masters: The University of Melbourne
Kevin Taddei: Edith Cowan University
Matthias Arnold: Duke University
Gabi Kastenmüller: Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health
Kwangsik Nho: Indiana University School of Medicine
Andrew J. Saykin: Indiana University School of Medicine
Xianlin Han: University of Texas Health Science Center at San Antonio
Rima Kaddurah-Daouk: Duke University
Ralph N. Martins: Edith Cowan University
John Blangero: The University of Texas Rio Grande Valley
Peter J. Meikle: Baker Heart and Diabetes Institute
Eric K. Moses: University of Tasmania

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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

Date: 2022
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DOI: 10.1038/s41467-022-30875-7

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