Disease coverage of human genome-wide association studies and pharmaceutical research and development

• Published in: Communications medicine Vol. 4; no. 1; pp. 195 - 11
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.10.2024; Springer Nature B.V; Nature Portfolio
• Subjects: 45/43; 631/208/205/2138; 692/308/153; Bioinformatics; Biomarkers; Classification; Disease; Drug development; Electronic health records; Genomes; Medical Subject Headings-MeSH; Medicine; Medicine & Public Health; Ontology; Pharmaceutical industry; R&D; Research & development; United States > US
• ISSN: 2730-664X; 2730-664X
• DOI: 10.1038/s43856-024-00625-5

Background 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. Methods 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. Results 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. Conclusions 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. Plain language summary The pharma industry has shown growing interest in the use of human genomic data to support drug development and reduce the risk of clinical-stage failure. We investigate the extent to which human diseases have been the subject of genetic studies, of pharmaceutical research and development, or both. We show that only a small proportion of all human diseases have an approved drug treatment and that less than half of all the diseases that are the subject of preclinical or clinical phase drug development have been investigated in genetic studies. In addition, approximately two-thirds of the diseases covered in genetic studies have yet to be investigated in drug development. These findings could help prioritize drug development efforts or genetic studies for diseases without effective treatments. Gordillo-Marañón et al. identify areas of convergence or divergence between genome-wide association studies (GWAS) and pharmaceutical research and development. They provide target-disease indication lists to prioritize drug development efforts in areas with genomic support, and diseases with few effective treatments that could benefit from GWAS.