153563 - Comprehensive genetic.pdf (6.31 MB)
Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease
journal contribution
posted on 2023-05-21, 13:51 authored by Cadby, G, Giles, C, Phillip MeltonPhillip Melton, Kevin Huynh, K, Mellett, NA, Duong, T, Nguyen, A, Cinel, M, Smith, A, Olshansky, G, Wang, T, Brozynska, M, Inouye, M, McCarthy, NS, Ariff, A, Hung, J, Hui, J, Beilby, J, Dube, M-P, Watts, GF, Shah, S, Wray, NR, Lim, WLF, Chatterjee, P, Martins, I, Laws, SM, Porter, T, Vacher, M, Bush, AI, Rowe, CC, Villemagne, VL, Ames, D, Masters, CL, Taddei, K, Arnold, M, Kastenmuller, G, Nho, K, Saykin, AJ, Han, X, Kaddurah-Daouk, R, Martins, RN, Blangero, J, Meikle, PJ, Eric MosesEric MosesWe 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.
History
Publication title
Nature communicationsVolume
13Article number
3124Number
3124Pagination
1-17ISSN
2041-1723Department/School
Menzies Institute for Medical ResearchPublisher
Nature Publishing GroupPlace of publication
LondonRights 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/.Repository Status
- Open