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. 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.

中文翻译：

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与年龄有关的疾病之间的常见遗传关联

年龄是许多疾病中常见的危险因素，但这种关系的分子基础尚不清楚。在这项研究中，我们从UK Biobank数据中的116种疾病中识别了4种疾病簇，这些疾病簇由其发病年龄特征定义，并且发现具有相同发病特征的疾病在遗传上更相似，这表明病因是常见的。疾病类别，同时发生或疾病因果关系并未解释这种相似性。四个疾病群中的两个分别从20岁和40岁开始增加发病的风险。他们都显示出与已知的衰老相关基因的关联，但是在功能富集和进化特征上有所不同。而且，它们都具有与年龄有关的表达和甲基化变化。