| アブストラクト | Reducing the burden of late-life morbidity requires an understanding of the mechanisms of ageing-related diseases (ARDs), defined as diseases that accumulate with increasing age. This has been hampered by the lack of formal criteria to identify ARDs. Here, we present a framework to identify ARDs using two complementary methods consisting of unsupervised machine learning and actuarial techniques, which we applied to electronic health records (EHRs) from 3,009,048 individuals in England using primary care data from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics admitted patient care dataset between 1 April 2010 and 31 March 2015 (mean age 49.7 years (s.d. 18.6), 51% female, 70% white ethnicity). We grouped 278 high-burden diseases into nine main clusters according to their patterns of disease onset, using a hierarchical agglomerative clustering algorithm. Four of these clusters, encompassing 207 diseases spanning diverse organ systems and clinical specialties, had rates of disease onset that clearly increased with chronological age. However, the ages of onset for these four clusters were strikingly different, with median age of onset 82 years (IQR 82-83) for Cluster 1, 77 years (IQR 75-77) for Cluster 2, 69 years (IQR 66-71) for Cluster 3 and 57 years (IQR 54-59) for Cluster 4. Fitting to ageing-related actuarial models confirmed that the vast majority of these 207 diseases had a high probability of being ageing-related. Cardiovascular diseases and cancers were highly represented, while benign neoplastic, skin and psychiatric conditions were largely absent from the four ageing-related clusters. Our framework identifies and clusters ARDs and can form the basis for fundamental and translational research into ageing pathways. |
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| 投稿者 | Kuan, Valerie; Fraser, Helen C; Hingorani, Melanie; Denaxas, Spiros; Gonzalez-Izquierdo, Arturo; Direk, Kenan; Nitsch, Dorothea; Mathur, Rohini; Parisinos, Constantinos A; Lumbers, R Thomas; Sofat, Reecha; Wong, Ian C K; Casas, Juan P; Thornton, Janet M; Hemingway, Harry; Partridge, Linda; Hingorani, Aroon D |
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| 組織名 | Institute of Health Informatics, University College London, London, UK.;v.kuan@ucl.ac.uk.;Health Data Research UK London, University College London, London, UK.;University College London British Heart Foundation Research Accelerator, London,;UK. v.kuan@ucl.ac.uk.;Institute of Healthy Ageing, Department of Genetics, Evolution and Environment,;University College London, London, UK.;Moorfields Eye Hospital, London, UK.;UK.;Alan Turing Institute, London, UK.;Department of Non-communicable Disease Epidemiology, London School of Hygiene and;Tropical Medicine, London, UK.;Barts Heart Centre, St Bartholomew's Hospital, London, UK.;School of Pharmacy, University College London, London, WC1N 1AX, UK.;Centre for Safe Medication Practice and Research, Department of Pharmacology and;Pharmacy, The University of Hong Kong, Pok Fu Lam, Hong Kong.;Department of Medicine, Brigham and Women's Hospital, Harvard Medical School,;Boston, MA, USA.;Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA;Boston Healthcare System, Boston, MA, USA.;European Molecular Biology Laboratory - European Bioinformatics Institute;EMBL-EBI, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, UK.;The National Institute for Health Research University College London Hospitals;Biomedical Research Centre, University College London, London, W1T 7DN, UK.;Max Planck Institute for Biology of Ageing, Cologne, Germany.;Institute of Cardiovascular Science, University College London, London, UK. |
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