Shu Le, Blencowe Montgomery, Yang Xia
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, United States.
Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, United States.
Front Cardiovasc Med. 2018 May 30;5:56. doi: 10.3389/fcvm.2018.00056. eCollection 2018.
The success of genome-wide association studies (GWAS) has significantly advanced our understanding of the etiology of coronary artery disease (CAD) and opens new opportunities to reinvigorate the stalling CAD drug development. However, there exists remarkable disconnection between the CAD GWAS findings and commercialized drugs. While this could implicate major untapped translational and therapeutic potentials in CAD GWAS, it also brings forward extensive technical challenges. In this review we summarize the motivation to leverage GWAS for drug discovery, outline the critical bottlenecks in the field, and highlight several promising strategies such as functional genomics and network-based approaches to enhance the translational value of CAD GWAS findings in driving novel therapeutics.
全基因组关联研究（GWAS）的成功显著推进了我们对冠状动脉疾病（CAD）病因的理解，并为重振停滞不前的CAD药物研发带来了新机遇。然而，CAD的GWAS研究结果与商业化药物之间存在显著脱节。虽然这可能意味着CAD的GWAS研究中存在尚未开发的重大转化和治疗潜力，但也带来了诸多技术挑战。在本综述中，我们总结了利用GWAS进行药物发现的动机，概述了该领域的关键瓶颈，并强调了几种有前景的策略，如功能基因组学和基于网络的方法，以提高CAD的GWAS研究结果在推动新型疗法方面的转化价值。
