Common genetic associations between age-related diseases

Age is a common risk factor in many diseases, but the molecular basis for this relationship is elusive. In this study we identified 4 disease clusters from 116 diseases in the 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 age 20 and 40 years respectively. They both showed an association with known aging-related genes, yet differed in functional enrichment and evolutionary profiles. We tested mutation accumulation and antagonistic pleiotropy theories of aging and found support for both. We also identified drug candidates for repurposing to target multiple age-dependent diseases with the potential to improve healthspan and alleviate multimorbidity and polypharmacy in the elderly.