Approved Research

A phenome-wide association and Mendelian Randomisation study of polygenic risk for Alzheimer's traits in UK Biobank

Lay summary

In the entire world, Alzheimer's disease is the number one cause of morbidity and mortality. The need for primary prevention has been reinforced by a clear decline in dementia prevalence and incidence that has been linked to earlier population-level investments like better vascular health and education. However, only a small number of modifiable risk factors were found, and if they were properly managed, they only reduced the risk of disease by 40%. There are still many unidentified risk factors. In this study, we seek to identify novel environmental factors that can be changed that influence the onset of Alzheimer's disease and to identify potential targets for interventions. To be more precise, we will 1) evaluate the impact of various environmental risk factors, such as lifestyles, comorbidity, medications, local environmental exposures, etc.; 2) investigate the potential interaction between these different factors; 3) identify people with genetic susceptibility and the way effect of risk factors can be modified by genetic variation; and 4) assess whether lifestyle factors play a role as potential effect modulator. A better understanding of the interplay between different modifiable environmental factors and the development of Alzheimer's disease is expected to provide new evidence for intervention target and facilitate more efficient prevention strategies and. This project may lead to a more holistic approach to personalized prevention and treatment, accounting for both individual-level factors and community-level environmental factors.