Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Atherosclerosis. 2012 Nov;225(1):1-10. doi: 10.1016/j.atherosclerosis.2012.05.015. Epub 2012 May 23.
Genome-wide association (GWA) studies on coronary artery disease (CAD) have been very successful, identifying a total of 32 susceptibility loci so far. Although these loci have provided valuable insights into the etiology of CAD, their cumulative effect explains surprisingly little of the total CAD heritability. In this review, we first highlight and describe the type of genetic variants potentially underlying the missing heritability of CAD: single nucleotide polymorphisms (SNPs) or structural variants, each of which may either be common or rare. Although finding missing heritability is important, we further argue in this review that it constitutes only a first step towards a fuller understanding of the etiology of CAD development. To close the gap between the genotype and phenotype, we propose a systems genetics approach in the post-GWA study era. This approach that integrates genetic, epigenetic, transcriptomic, proteomic, metabolic and intermediate outcome variables has potential to significantly aid the understanding of CAD etiology.
全基因组关联（GWA）研究在冠状动脉疾病（CAD）方面非常成功，迄今为止总共确定了 32 个易感位点。尽管这些位点为 CAD 的病因学提供了有价值的见解，但它们的累积效应令人惊讶地仅解释了 CAD 总遗传率的一小部分。在这篇综述中，我们首先强调并描述了潜在导致 CAD 遗传缺失的遗传变异类型：单核苷酸多态性（SNP）或结构变异，它们中的每一种可能是常见的或罕见的。尽管发现遗传缺失很重要，但我们在这篇综述中进一步认为，这只是对 CAD 发展病因学更全面理解的第一步。为了缩小基因型和表型之间的差距，我们在 GWA 研究之后的时代提出了一种系统遗传学方法。这种方法整合了遗传、表观遗传、转录组、蛋白质组、代谢和中间结果变量，有可能显著帮助我们理解 CAD 的病因学。
