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

Citation

Cadby, G and Giles, C and Melton, PE and Kevin Huynh, K and Mellett, NA and Duong, T and Nguyen, A and Cinel, M and Smith, A and Olshansky, G and Wang, T and Brozynska, M and Inouye, M and McCarthy, NS and Ariff, A and Hung, J and Hui, J and Beilby, J and Dube, M-P and Watts, GF and Shah, S and Wray, NR and Lim, WLF and Chatterjee, P and Martins, I and Laws, SM and Porter, T and Vacher, M and Bush, AI and Rowe, CC and Villemagne, VL and Ames, D and Masters, CL and Taddei, K and Arnold, M and Kastenmuller, G and Nho, K and Saykin, AJ and Han, X and Kaddurah-Daouk, R and Martins, RN and Blangero, J and Meikle, PJ and Moses, EK, Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease, Nature communications, 13, (1) Article 3124. ISSN 2041-1723 (2022) [Refereed Article]


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Copyright Statement

The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/.

Official URL: https://www.nature.com/articles/s41467-022-30875-7

DOI: doi:10.1038/s41467-022-30875-7

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 < 1 x 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.

Item Details

Item Type:Refereed Article
Keywords:Lipidomics, GWAS, Busselton, Family Study,
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Gene mapping
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Public health (excl. specific population health) not elsewhere classified
UTAS Author:Melton, PE (Dr Phillip Melton)
UTAS Author:Moses, EK (Professor Eric Moses)
ID Code:153563
Year Published:2022
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-09-26
Last Modified:2022-11-01
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