Objective Electronic Health Records (EHR) are a rich source of information on human diseases, but the information is variably structured, fragmented, curated using different coding systems and collected for purposes other than medical research. We describe an approach for developing, validating and sharing reproducible phenotypes from national structured EHR in the United Kingdom (UK) with applications for translational research. Materials and MethodsWe implemented a rule-based phenotyping framework, with up to six approaches of validation. We applied our framework to a sample of 15 million individuals in a national EHR data source (population-based primary care, all ages) linked to hospitalization and death records in England. Data comprised continuous measurements e.g. blood pressure, medication information and coded diagnoses, symptoms, procedures and referrals, recorded using five controlled clinical terminologies: a) Read (primary care, subset of SNOMED-CT), b) International Classification of Diseases 9th/10th Revision (ICD-9, ICD-10, secondary care diagnoses and cause of mortality), c) OPCS Classification of Interventions and Procedures (OPCS-4, hospital surgical procedures), and d) DM+D prescription codes. Results Using the CALIBER phenotyping framework, we created algorithms for 51 diseases, syndromes, biomarkers and lifestyle risk factors and provide up to six validation approaches. The EHR phenotypes are curated in the open-access CALIBER Portal (https://www.caliberresearch.org/portal) and have been used by 40 national/international research groups in 60 peer-reviewed publications.
Genetic, environmental and pharmacological interventions into the aging process can confer resistance to a multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that mechanisms of aging might contribute to patterns of multimorbidity in humans, and hence could be targeted to prevent multiple conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation, and found strong, non-random associations between age-related diseases and aging mechanisms, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signalling pathway and activity of the ERK1/2 pathway played a significant role across multiple aging mechanisms and multiple, diverse age-related diseases. Mechanisms of aging therefore contribute to multiple age-related diseases and to patterns of human age-related multimorbidity, and could potentially be targeted to prevent more than one age-related condition in the same patient.
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