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.

中文翻译：

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对全基因组关联数据的分析突出了精神病学中药物重新定位的候选人。

在过去的十年中，随着全基因组关联研究（GWAS）的到来，精神疾病遗传学的知识迅速发展。但是，在利用这些数据揭示新疗法方面取得的进展较少。在这里，我们通过比较从GWAS数据推算出的转录组与来自Connectivity Map数据库的药物诱导的基因表达谱，提出了一种药物重新定位的框架，并将这种方法应用于七种精神疾病。我们找到了许多重新定位的候选人，其中许多人得到了临床前或临床证据的支持。对于许多疾病的重新定位候选者，对于临床试验中考虑的已知精神科药物或疗法，也大大丰富了。例如，精神分裂症的候选人富含抗精神病药，而双相情感障碍者则富含抗精神病药和抗抑郁药。这些发现为GWAS数据在指导药物开发中的实用性提供了支持。