Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL.
Circ Genom Precis Med. 2018 Feb;11(2). Epub 2018 Jan 30.
Genome-wide association studies (GWASs) have implicated many human genomic loci in the development of complex traits. The loci identified by these studies are potentially involved in novel pathways that contribute to disease pathophysiology. However, eventual therapeutic targeting of these pathways relies on bridging the gap between genetic association and function, a task that first requires validation of causal genetic variants, casual genes, and directionality of effect. Executing this task requires basic knowledge of interpreting GWAS results and prioritizing candidates for further study, in addition to understanding the experimental methods available for evaluating candidate variants. Here we review the basic genetic principles of genome-wide association studies, the computational and experimental tools used for identifying causal variants and genes, and salient illustrative examples of how cardiovascular loci have undergone functional investigation.
全基因组关联研究（GWAS）已经在复杂性状的发展中涉及到许多人类基因组位点。这些研究中确定的位点可能涉及到新的途径，有助于疾病的病理生理学。然而，最终对这些途径进行治疗靶向依赖于弥合遗传关联和功能之间的差距，这一任务首先需要验证因果遗传变异、因果基因和效应的方向。执行这一任务需要基本的解释 GWAS 结果和优先考虑进一步研究候选者的知识，以及了解评估候选变异的可用实验方法。在这里，我们回顾了全基因组关联研究的基本遗传原理，用于识别因果变异和基因的计算和实验工具，以及心血管位点如何进行功能研究的突出实例。
