| Application: | 36509, Role of vascular risk factors, genes and lifestyle in the risk of cerebrovascular disease, cognitive decline and dementia. |
| Title: | Genome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants |
| Size: | 742219 B |
| Archived: | 29 Jul 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 3694
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Notes
Cerebral small vessel disease is a major cause of stroke and dementia, but its genetic basis is incompletely understood. We perform a genetic study of three MRI markers of the disease in UK Biobank imaging data and other sources: white matter hyperintensities (N = 42,310), fractional anisotropy (N = 17,663) and mean diffusivity (N = 17,467). Our aim is to better understand the disease pathophysiology. Across the three traits, we identify 31 loci, of which 21 were previously unreported. We perform a transcriptome-wide association study to identify associations with gene expression in relevant tissues, identifying 66 associated genes across the three traits. This genetic study provides insights into the understanding of the biological mechanisms underlying small vessel disease.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 |
|---|---|---|---|
| 3866 | 36509 | Association of common genetic variants with brain microbleeds | 28 Sep 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 |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 3695 | Genome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants | Elodie Persyn (+5) | 2020 | Nature Communications |
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