Notes
The purpose of our application is to elucidate the biological pathways through which the various markers of health and information available in the biobank dataset are linked with acute cerebrovascular events, magnetic resonance imaging features of cerebrovascular disease, cognitive decline and vascular dementia. This paper investigates the presence of microbleeds (as seen on MRI) as a function of genetic variants, particularly those that relate to small vessel disease and stroke. UK Biobank was one of a number of datasets included in the study. It was found that Genetic variants in the APOE region are associated with the presence of microbleeds, most likely due to the APOE e4 allele count related to a higher number of strictly lobar microbleeds. Genetic predisposition to small vessel disease, as measured by other markers of small vessel disease, confers risk of microbleeds, indicating genetic overlap with other cerebral small vessel disease markers. This study contributes to our understanding of how genetics contributes to vascular pathologies.
Application 36509
Role of vascular risk factors, genes and lifestyle in the risk of cerebrovascular disease, cognitive decline and dementia.
Cerebrovascular disease is a strong risk factor for cognitive decline and subsequently dementia. Vascular risk factors, genes and lifestyle have been associated with both cerebrovascular disease and cognitive decline, but the underlying pathophysiological mechanisms are complex. Our study aims to integrate and analyse the extensive clinical, epidemiological, genetic and imaging data available, in order to
- elucidate the biological pathways through which the vascular, (novel) genetic and lifestyle factors interact and are linked with acute cerebrovascular events, magnetic resonance imaging features of cerebrovascular disease, cognitive decline and dementia
- to what extend demographic characteristics and prescribed medication influence these relations An aim of UK Biobank is the reliable assessment of different causes of disease. The extensive clinical, epidemiological and genetic data available in UK Biobank provide the opportunity to increase our insight in the interplay and causality of different risk factors in the pathophysiological mechanisms underlying cerebrovascular disease or dementia. Previously, small sample sizes of typical cohort studies have limited the possibility to perform these analyses. We will test for associations between the risk We will test for associations between the risk factors of interests and the phenotypes under study.
We aim to identify novel genetic risk variants for the phenotypes under study by performing genome-wide association studies and statistically more efficient methods including pleiotropy-based methods. In addition we will do a comprehensive computational assessment of how the risk factors of interest interact in influencing the phenotypes under study and explore any mediating relationships. Data from the full cohort will be required (both males and females).
Lead investigator: | Professor Hugh Markus |
Lead institution: | University of Cambridge |
3 related Returns
Return ID | App ID | Description | Archive Date |
3694 | 36509 | Genome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants | 29 Jul 2021 |
3282 | 36509 | Network Efficiency Mediates the Relationship Between Vascular Burden and Cognitive Impairment | 6 Apr 2021 |
2320 | 36509 | Prevalence and Risk Factors of Cerebral Microbleeds | 9 Feb 2024 |