Cerebral small vessel disease and Alzheimer's disease susceptibility: a genome-wide interaction study
Approved Research ID: 56197
Approval date: September 1st 2020
Alzheimer's disease (AD) is the commonest cause of dementia, in which patients will experience a progressive decline in cognition, language, memory, and physical ability. People with dementia due to AD in life are typically found to have multiple additional pathologies at autopsy. In particular, cerebral small vessel disease (SVD), is one of the commonest in the majority late-onset cases of AD (the more common form of AD and typically begins in patients age 65 and older). Cerebral SVD is a type of vascular lesion in the brain, with certain characteristic impairments in brain structures that can be assessed via magnetic resonance imaging (MRI). On the other hand, conventional genome-wide association studies (GWAS), a type of genetics analysis that surveys the whole genome for genetic variants associated with certain disease or physical traits, revealed ~21 genetic variants associated with AD. However, mechanisms underlying AD onset and progression remain unresolved.
Conventional GWAS also focus on genetic variants with main effects and often eliminate variants that are likely to show conditional effects. A novel approach is to conduct a genome-wide interaction study (GWIS) which focuses on important interaction effects. Here, I will survey the human genome for interactions between SVD brain imaging and genetic characteristics, which contribute together to increase the risk of AD diagnosis, and to AD-associated brain imaging and cognitive disease characteristics. We aim to conduct this GWIS over the course of 3 years, in which we will conduct quality control and sophisticated statistical analyses for the anticipated massive datasets of brain imaging, cognitive, and genetic data. The pathological heterogeneity in AD has posed a tremendous challenge in developing treatments for the disease. Via analyzing the above mentioned data variables in individuals with normal cognitive status and demented populations in the UK Biobank, our goal is to disentangle the roles of heterogeneous pathological factors underlying the clinical symptoms in order to overcome the tremendous challenge this poses in the quest for effective treatments.