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There is a significant symptom overlap between the two disorders\u2014psychosis is seen in 50% of patients with Alzheimer\u2019s disease and cognitive impairment is a key feature of schizophrenia. Whether these overlapping clinical presentations reflect shared aetiology is unclear. Therefore, we aimed to model the genetic correlation between Alzheimer\u2019s disease, schizophrenia and their shared risk factors using genomic structural equation modelling to identify potentially overlapping biological pathways between these traits. We measured genetic correlation between Alzheimer\u2019s disease, schizophrenia and 13 shared risk factors, including body fat percentage, less education, alcohol intake, insomnia, loneliness, less social\/leisure activity, major depression, mean arterial pressure, smoking, socioeconomic deprivation, low-density lipoprotein cholesterol, eye problems and type 2 diabetes mellitus. Schizophrenia and Alzheimer\u2019s disease were not significantly genetically correlated but were both significantly associated with loneliness. Colocalization suggested that the association between loneliness and Alzheimer\u2019s disease was predominantly driven by a shared causal variant on Chromosome 11. Factor analysis of shared risk factors produced four latent factors representing clusters of shared genetics between socioeconomic traits, psychiatric traits, cardiometabolic traits and smoking-related traits. Both Alzheimer\u2019s disease and schizophrenia were significantly associated with the socioeconomic latent factor. Although there is little direct genetic overlap between schizophrenia and Alzheimer\u2019s disease, loneliness may play an important role in the association between these two disorders. In addition, the shared genetics between socioeconomic traits may affect susceptibility to both Alzheimer\u2019s disease and schizophrenia to a greater extent than trait-specific pathways.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf112","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T04:07:26Z","timestamp":1744258046000},"source":"Crossref","is-referenced-by-count":5,"title":["Examining the genetic relationship between Alzheimer\u2019s disease, schizophrenia and their shared risk factors using genomic structural equation modelling"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-9745","authenticated-orcid":false,"given":"In\u00eas","family":"Almeida e Sousa","sequence":"first","affiliation":[{"name":"Unit for Psychological Medicine, Wolfson Institute of Population Health, Queen Mary University of London , London EC1M 6BQ ,","place":["UK"]},{"name":"Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London , London EC1M 6BQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Grotzinger","sequence":"additional","affiliation":[{"name":"Institute for Behavioral Genetics, University of Colorado Boulder , Boulder, CO 80303 ,","place":["USA"]},{"name":"Department of Psychology and Neuroscience, University of Colorado Boulder , Boulder, CO 80309 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy M","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Institute for Behavioral Genetics, University of Colorado Boulder , Boulder, CO 80303 ,","place":["USA"]},{"name":"Department of Psychology and Neuroscience, University of Colorado Boulder , Boulder, CO 80309 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Breunig","sequence":"additional","affiliation":[{"name":"Institute for Behavioral Genetics, University of Colorado Boulder , Boulder, CO 80303 ,","place":["USA"]},{"name":"Department of Psychology and Neuroscience, University of Colorado Boulder , Boulder, CO 80309 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R","family":"Marshall","sequence":"additional","affiliation":[{"name":"Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London , London EC1M 6BQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ania","family":"Korszun","sequence":"additional","affiliation":[{"name":"Unit for Psychological Medicine, Wolfson Institute of Population Health, Queen Mary University of London , London EC1M 6BQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle F","family":"Foote","sequence":"additional","affiliation":[{"name":"Unit for Psychological Medicine, Wolfson Institute of Population Health, Queen Mary University 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