Abstract
AbstractAdvancing age is the greatest risk factor for developing multiple age-related diseases. Therapeutic approaches targeting the underlying pathways of ageing, rather than individual diseases, may be an effective way to treat and prevent age-related morbidity while reducing the burden of polypharmacy. We harness the Open Targets Genetics Portal to perform a systematic analysis of nearly 1,400 genome-wide association studies (GWAS) mapped to 34 age-related diseases and traits, identifying genetic signals that are shared between two or more of these traits. Using locus-to-gene (L2G) mapping, we identify 995 targets with shared genetic links to age-related diseases and traits, which are enriched in mechanisms of ageing and include known ageing and longevity-related genes. Of these 995 genes, 128 are the target of an approved or investigational drug, 526 have experimental evidence of binding pockets or are predicted to be tractable, and 341 have no existing tractability evidence, representing underexplored genes which may reveal novel biological insights and therapeutic opportunities. We present these candidate targets for exploration and prioritisation in a web application.
Publisher
Springer Science and Business Media LLC
Subject
Library and Information Sciences,Statistics, Probability and Uncertainty,Computer Science Applications,Education,Information Systems,Statistics and Probability
Reference73 articles.
1. Partridge, L., Deelen, J. & Slagboom, P. E. Facing up to the global challenges of ageing. Nature 561, 45–56 (2018).
2. Office for National Statistics. National population projections: 2020-based interim. https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationprojections/bulletins/nationalpopulationprojections/2020basedinterim#toc (2022).
3. Great Britain. Parliament. House of Lords. Science and Technology Committee. Ageing: Science, Technology and Healthy Living : 1st Report of Session 2019-21. (Dandy Booksellers Limited, 2021).
4. NIHR Dissemination Centre. Multi-morbidity predicted to increase in the UK over the next 20 years. https://evidence.nihr.ac.uk/alert/multi-morbidity-predicted-toincrease-in-the-uk-over-the-next-20-years, https://doi.org/10.3310/signal-00572 (2018).
5. Masnoon, N., Shakib, S., Kalisch-Ellett, L. & Caughey, G. E. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 17, 230 (2017).
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献