Analysis of genome-wide association data highlights candidates for drug repositioning in psychiatry
Analysis of genome-wide association data highlights candidates for drug repositioning in psychiatry
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DOI：
10.1038/nn.4618
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发表时间：
2017-10-01
影响因子：
25
通讯作者：
Sham, Pak-Chung
中科院分区：
文献类型：
--
作者：
So, Hon-Cheong;Chau, Carlos Kwan-Long;Sham, Pak-Chung
随着全基因组关联研究（GWAS）的出现，精神疾病遗传学的知识在过去十年中迅速发展。然而，在利用这些数据揭示新疗法方面取得的进展较少。在这里，我们提出了一个框架，通过比较转录组插补从GWAS数据与药物诱导的基因表达谱的连接地图数据库，并将这种方法应用于7种精神疾病的药物重新定位。我们发现了许多重新定位的候选者，许多都得到了临床前或临床证据的支持。许多疾病的重新定位候选者也显著丰富了临床试验中考虑的已知精神病药物或疗法。例如，精神分裂症的候选人富含抗精神病药物，而双相情感障碍的候选人富含抗精神病药物和抗抑郁药物。这些发现为GWAS数据在指导药物发现方面的有用性提供了支持。
Knowledge of psychiatric disease genetics has advanced rapidly during the past decade with the advent of genome-wide association studies (GWAS). However, less progress has been made in harnessing these data to reveal new therapies. Here we propose a framework for drug repositioning by comparing transcriptomes imputed from GWAS data with drug-induced gene expression profiles from the Connectivity Map database and apply this approach to seven psychiatric disorders. We found a number of repositioning candidates, many supported by preclinical or clinical evidence. Repositioning candidates for a number of disorders were also significantly enriched for known psychiatric medications or therapies considered in clinical trials. For example, candidates for schizophrenia were enriched for antipsychotics, while those for bipolar disorder were enriched for both antipsychotics and antidepressants. These findings provide support for the usefulness of GWAS data in guiding drug discovery.