Comprehensive genomic profiling in Alzheimer's disease (AD) and other dementias will become pivotal in selecting targeted therapies based on an individual risk profile. The Genetics working group addresses this challenge by bringing together genetic data from over 25 cohorts to establish disease risk profiles using polygenic risk sores. Comparable work in other diseases, such as breast or prostate cancer, have shown enhanced utility for clinicians in predicting the development and progression of these diseases, by integrating polygenic risk scores into risk models. These links are, however, currently underexploited for clinical diagnostic practice in AD and dementia. Genetic data from collaborating DPUK cohorts will be used to address the genetic variability of dementia. Using genetic expertise led from the UK DRI, genetic information will be linked with clinical presentation at different stages of dementia and integrated with additional factors, such as geographical and ethnic diversity, to fully capture heterogeneity of common dementias. To achieve high diagnostic accuracy, genetic risk scoring will be linked with other phenotypes, biomarkers, clinical and environmental information, and tested for its prediction accuracy in specific groups of people targeting specific functional mechanisms of disease development. Analyses will be conducted within the DPUK Data Portal. This project will establishing a technological platform and best practices for national and international collaboration between clinicians, geneticists, biostatisticians, data scientists and wet lab scientists. The project will 1) unify and harmonise all genetic data available via the DPUK Data Portal; 2) derive genetic risk scores with the latest genome-wide association results for all DPUK cohorts in a unified way; 3) integrate genetic risk scores with clinical data with the aim to obtain a complete map linking genetic profiles and disease manifestations across the entire spectrum of dementia. By maximally exploiting demographic, clinical, and research data and linking them to individual genetic risk scores, this project will establish a roadmap towards precision medicine for Alzheimer's disease and other dementias. The unified genetic data across cohorts available in DPUK, will be an aid to refine inclusion criteria for future clinical trials and ultimately translate into guidance for personalized healthcare decisions.