Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease.
Nat Commun
; 13(1): 3124, 2022 06 06.
Article
in En
| MEDLINE
| ID: mdl-35668104
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 â¼456,000 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Coronary Artery Disease
Type of study:
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limits:
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2022
Document type:
Article
Affiliation country:
Australia