Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity.
Author
West, Clare EKarim, Mohd
Falaguera, Maria J
Speidel, Leo
Green, Charlotte J
Logie, Lisa
Schwartzentruber, Jeremy
Ochoa, David
Lord, Janet M
Ferguson, Michael A J
Bountra, Chas
Wilkinson, Graeme F
Vaughan, Beverley
Leach, Andrew R
Dunham, Ian
Marsden, Brian D
Publication date
2023-09-25Subject
Genetics
Metadata
Show full item recordAbstract
Advancing 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.Citation
West CE, Karim M, Falaguera MJ, Speidel L, Green CJ, Logie L, Schwartzentruber J, Ochoa D, Lord JM, Ferguson MAJ, Bountra C, Wilkinson GF, Vaughan B, Leach AR, Dunham I, Marsden BD. Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity. Sci Data. 2023 Sep 25;10(1):655. doi: 10.1038/s41597-023-02513-4. PMID: 37749083; PMCID: PMC10520009.Type
ArticlePMID
37749083Journal
Scientific DataPublisher
Nature Researchae974a485f413a2113503eed53cd6c53
10.1038/s41597-023-02513-4