Gordillo-Marañón María, Schmidt Amand F, Warwick Alasdair, Tomlinson Chris, Ytsma Cai, Engmann Jorgen, Torralbo Ana, Maclean Rory, Sofat Reecha, Langenberg Claudia, Shah Anoop D, Denaxas Spiros, Pirmohamed Munir, Hemingway Harry, Hingorani Aroon D, Finan Chris
Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, United Kingdom.
Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands.
Commun Med (Lond). 2024 Oct 8;4(1):195. doi: 10.1038/s43856-024-00625-5.
Despite the growing interest in the use of human genomic data for drug target identification and validation, the extent to which the spectrum of human disease has been addressed by genome-wide association studies (GWAS), or by drug development, and the degree to which these efforts overlap remain unclear.
In this study we harmonize and integrate different data sources to create a sample space of all the human drug targets and diseases and identify points of convergence or divergence of GWAS and drug development efforts.
We show that only 612 of 11,158 diseases listed in Human Disease Ontology have an approved drug treatment in at least one region of the world. Of the 1414 diseases that are the subject of preclinical or clinical phase drug development, only 666 have been investigated in GWAS. Conversely, of the 1914 human diseases that have been the subject of GWAS, 1121 have yet to be investigated in drug development.
We produce target-disease indication lists to help the pharmaceutical industry to prioritize future drug development efforts based on genetic evidence, academia to prioritize future GWAS for diseases without effective treatments, and both sectors to harness genetic evidence to expand the indications for licensed drugs or to identify repurposing opportunities for clinical candidates that failed in their originally intended indication.
尽管利用人类基因组数据进行药物靶点识别和验证的兴趣日益浓厚，但全基因组关联研究（GWAS）或药物开发在多大程度上涵盖了人类疾病谱，以及这些努力的重叠程度仍不明确。
在本研究中，我们整合并统一了不同的数据源，以创建一个包含所有人类药物靶点和疾病的样本空间，并确定GWAS和药物开发工作的交汇点或分歧点。
我们发现，在《人类疾病本体论》列出的11158种疾病中，只有612种在世界至少一个地区有获批的药物治疗。在处于临床前或临床阶段药物开发的1414种疾病中，只有666种在GWAS中得到研究。相反，在1914种已进行GWAS研究的人类疾病中，有1121种尚未在药物开发中得到研究。
我们生成了靶点-疾病适应症列表，以帮助制药行业根据遗传证据确定未来药物开发工作的优先级，帮助学术界确定针对尚无有效治疗方法的疾病开展未来GWAS的优先级，并帮助两个领域利用遗传证据来扩大已获批药物的适应症，或为在其最初预期适应症中失败的临床候选药物确定重新利用的机会。
