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 × 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.
RAS ID
43321
Document Type
Journal Article
Date of Publication
12-1-2022
Volume
13
Issue
1
Funding Information
National Health and Medical Research Council of Australia Grants: 1101320, 1157607, APP1161706 / Edith Cowan University (ECU) /
Further funding information available at:
PubMed ID
35668104
School
School of Medical and Health Sciences / Centre for Precision Health
Grant Number
NHMRC Numbers : 1101320, 1157607, APP1161706
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Publisher
Nature
Identifier
Wei Ling Florence Lim
https://orcid.org/0000-0002-8988-2147
Ian Martins
https://orcid.org/0000-0002-2390-1501
Simon M. Laws
https://orcid.org/0000-0002-4355-7082
Tenielle Porter
https://orcid.org/0000-0002-7887-6622
Kevin Taddei
https://orcid.org/0000-0002-8106-7957
Ralph N. Martins
Recommended Citation
Cadby, G., Giles, C., Melton, P. E., Huynh, K., Mellett, N. A., Duong, T., Nguyen, A., Cinel, M., Smith, A., Olshansky, G., Wang, T., Brozynska, M., Inouye, M., McCarthy, N. S., Ariff, A., Hung, J., Hui, J., Beilby, J., Dubé, M. P., Watts, G. F., Shah, S., Wray, N. R., Lim, W. L., Chatterjee, P., Martins, I., Laws, S. M., Porter, T., Vacher, M., Bush, A. I., Rowe, C. C., Villemagne, V. L., Ames, D., Masters, C. L., Taddei, K., Arnold, M., Kastenmüller, G., Nho, K., Saykin, A. J., Han, X., Kaddurah-Daouk, R., Martins, R. N., Blangero, J., Meikle, P. J., & Moses, E. K. (2022). Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease. DOI: https://doi.org/10.1038/s41467-022-30875-7
Comments
Cadby, G., Giles, C., Melton, P. E., Huynh, K., Mellett, N. A., Duong, T., ... & Moses, E. K. (2022). Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease. Nature Communications, 13(1), 1-17.
https://doi.org/10.1038/s41467-022-30875-7