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Common genetic associations between age-related diseases

Dönertaş, HM; Fabian, DK; Fuentealba, M; Partridge, L; Thornton, JM; (2021) Common genetic associations between age-related diseases. Nature Aging , 1 (4) pp. 400-412. 10.1038/s43587-021-00051-5. Green open access

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Abstract

Age is a common risk factor in many diseases, but the molecular basis for this relationship is elusive. In this study we identified four disease clusters from 116 diseases in UK Biobank data, defined by their age-of-onset profiles, and found that diseases with the same onset profile are genetically more similar, suggesting a common etiology. This similarity was not explained by disease categories, co-occurrences or disease cause–effect relationships. Two of the four disease clusters had an increased risk of occurrence from ages 20 and 40 years, respectively. They both showed an association with known aging-related genes, yet differed in functional enrichment and evolutionary profiles. Moreover, they both had age-related expression and methylation changes. We also tested mutation accumulation and antagonistic pleiotropy theories of aging and found support for both.

Type: Article
Title: Common genetic associations between age-related diseases
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s43587-021-00051-5
Publisher version: https://doi.org/10.1038/s43587-021-00051-5
Language: English
Additional information: This version is the author accepted manuscript. This research was funded in whole, or in part, by the Wellcome Trust (098565/Z/12/Z). For the purpose of Open Access, the authors have applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission.
Keywords: Aging; age-related disease; GWAS; UK Biobank; mutation accumulation; antagonistic pleiotropy
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10152609
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