Reay William R, Cairns Murray J
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia.
Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
Nat Rev Genet. 2021 Oct;22(10):658-671. doi: 10.1038/s41576-021-00387-z. Epub 2021 Jul 23.
Genome-wide association studies (GWAS) have revealed important biological insights into complex diseases, which are broadly expected to lead to the identification of new drug targets and opportunities for treatment. Drug development, however, remains hampered by the time taken and costs expended to achieve regulatory approval, leading many clinicians and researchers to consider alternative paths to more immediate clinical outcomes. In this Review, we explore approaches that leverage common variant genetics to identify opportunities for repurposing existing drugs, also known as drug repositioning. These approaches include the identification of compounds by linking individual loci to genes and pathways that can be pharmacologically modulated, transcriptome-wide association studies, gene-set association, causal inference by Mendelian randomization, and polygenic scoring.
全基因组关联研究（GWAS）揭示了有关复杂疾病的重要生物学见解，人们普遍期望这些见解能带来新药物靶点的识别以及治疗机会。然而，药物开发仍因获得监管批准所需的时间和成本而受阻，这使得许多临床医生和研究人员考虑采用替代途径以实现更直接的临床疗效。在本综述中，我们探讨利用常见变异遗传学来识别现有药物重新用途机会的方法，即药物重新定位。这些方法包括通过将单个基因座与可进行药理调节的基因和通路相联系来识别化合物、全转录组关联研究、基因集关联、孟德尔随机化因果推断以及多基因评分。
