Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity
Abstract 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 polyph...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Data |
| Online Access: | https://doi.org/10.1038/s41597-023-02513-4 |
| _version_ | 1797578198732505088 |
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| author | Clare E. West Mohd Karim Maria J. Falaguera Leo Speidel Charlotte J. Green Lisa Logie Jeremy Schwartzentruber David Ochoa Janet M. Lord Michael A. J. Ferguson Chas Bountra Graeme F. Wilkinson Beverley Vaughan Andrew R. Leach Ian Dunham Brian D. Marsden |
| author_facet | Clare E. West Mohd Karim Maria J. Falaguera Leo Speidel Charlotte J. Green Lisa Logie Jeremy Schwartzentruber David Ochoa Janet M. Lord Michael A. J. Ferguson Chas Bountra Graeme F. Wilkinson Beverley Vaughan Andrew R. Leach Ian Dunham Brian D. Marsden |
| author_sort | Clare E. West |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T22:19:40Z |
| format | Article |
| id | doaj.art-bd0a4e946edc4e929857d3968138af9c |
| institution | Directory Open Access Journal |
| issn | 2052-4463 |
| language | English |
| last_indexed | 2024-03-10T22:19:40Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Data |
| spelling | doaj.art-bd0a4e946edc4e929857d3968138af9c2023-11-19T12:20:26ZengNature PortfolioScientific Data2052-44632023-09-0110111310.1038/s41597-023-02513-4Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidityClare E. West0Mohd Karim1Maria J. Falaguera2Leo Speidel3Charlotte J. Green4Lisa Logie5Jeremy Schwartzentruber6David Ochoa7Janet M. Lord8Michael A. J. Ferguson9Chas Bountra10Graeme F. Wilkinson11Beverley Vaughan12Andrew R. Leach13Ian Dunham14Brian D. Marsden15Centre for Medicines Discovery, University of OxfordOpen Targets, Wellcome Genome CampusOpen Targets, Wellcome Genome CampusFrancis Crick InstituteDrug Discovery Unit, University of DundeeDrug Discovery Unit, University of DundeeEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome CampusOpen Targets, Wellcome Genome CampusMRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of BirminghamDrug Discovery Unit, University of DundeeCentre for Medicines Discovery, University of OxfordMedicines Discovery CatapultCentre for Medicines Discovery, University of OxfordOpen Targets, Wellcome Genome CampusOpen Targets, Wellcome Genome CampusCentre for Medicines Discovery, University of OxfordAbstract 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.https://doi.org/10.1038/s41597-023-02513-4 |
| spellingShingle | Clare E. West Mohd Karim Maria J. Falaguera Leo Speidel Charlotte J. Green Lisa Logie Jeremy Schwartzentruber David Ochoa Janet M. Lord Michael A. J. Ferguson Chas Bountra Graeme F. Wilkinson Beverley Vaughan Andrew R. Leach Ian Dunham Brian D. Marsden Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity Scientific Data |
| title | Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity |
| title_full | Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity |
| title_fullStr | Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity |
| title_full_unstemmed | Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity |
| title_short | Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity |
| title_sort | integrative gwas and co localisation analysis suggests novel genes associated with age related multimorbidity |
| url | https://doi.org/10.1038/s41597-023-02513-4 |
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