Dementia arises from complex interactions between genetic susceptibility, environmental exposures, and biological pathways. Although numerous genetic loci have been associated with dementia, their functional impact, penetrance, and relationship to modifiable risk factors remain incompletely understood. This project aims to investigate the interplay between genetic, environmental, and immunological factors in dementia using GWAS, sequencing, and biomarker data from the UK Biobank, integrated with epidemiological, cognitive, and imaging information. Analyses will explore how genetic and immunological profiles relate to dementia risk, age at onset, and clinical or biological subtypes, and how these associations may be modified by cardiovascular, metabolic, psychosocial, or sex-specific factors. Both genetics-first and biomarker-first approaches will be employed to identify mechanisms linking molecular variation to disease expression. Pleiotropic and shared biological pathways will also be examined, as well as the potential to identify novel or under-recognized variants contributing to dementia or related phenotypes. The findings aim to enhance understanding of disease mechanisms, improve risk prediction, and inform precision prevention strategies.
