School of Population and Global Health, University of Western Australia, Crawley, WA, Australia.
Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Nat Commun. 2022 Jun 6;13(1):3124. doi: 10.1038/s41467-022-30875-7.
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), 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.
我们整合了脂质组学和基因组学，以揭示脂质代谢的遗传结构，并确定与冠心病（CAD）机制途径中假定的脂质种类相关的遗传变异。我们在来自 4492 名 Busselton 健康研究个体的血清中定量了 596 种脂质。发现的 GWAS 确定了 3361 个独立的脂质 - 基因座关联，涉及 667 个基因组区域（479 个以前未报道过），在两个独立的队列中得到了验证。荟萃分析显示，与脂质种类相关的还有另外 70 个独立的基因组区域。我们确定了与 186 个基因组位点相关的 134 个 CAD 脂质内表型。在来自英国生物库的约 456000 名个体中评估了独立脂质 - 基因座与冠状动脉粥样硬化之间的关联。在表现出关联证据的 53 个脂质基因座中（P < 1×10），43 个基因座与至少一个脂质内表型相关。这些发现说明了综合生物学在研究动脉粥样硬化和 CAD 病因学方面的价值，对其他复杂疾病也有影响。
