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 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. Using genetic and demographic data from the UK Biobank, the authors clustered 116 common diseases based on their age-of-onset profiles and found increased genetic similarity within clusters, suggesting common etiologies. Two of the four disease clusters were associated with aging-related genes but differed in functional enrichment and evolutionary profiles.