| Application: | 17689, Genetic, environmental and lifestyle predictors of brain/cognitive-related outcomes. |
| Title: | PCSK9 genetic variants and cognitive abilities: a large-scale Mendelian randomization study |
| Size: | 59115 B |
| Archived: | 11 May 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 3404
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Notes
PCSK9 inhibitors are an effective medication for lowering low-density lipoprotein levels, and their use has been associated with lower risk of poor cardiometabolic health. Some questions remain from trial data, however, relating to whether their use may have cognitive side-effects (e.g. memory). We used genetic variation in the PCSK9 gene to mimic use of these inhibitors in generally healthy middle-aged to older adults. We found limited evidence of association between the PCSK9 genetic risk score and worse cognitive scores; overall, pharmacovigilance is recommended.Application 17689
Genetic, environmental and lifestyle predictors of brain/cognitive-related outcomes.
The project aims to integrate genetic, biomarker, brain imaging and cognitive/mood data to give a complete 'picture' of what predicts, mediates and moderates worse mental ability and mood disorder in UK Biobank, cross-sectionally and prospectively using follow-up data. We will research this question using UK Biobank cognitive test, brain MRI (structural and functional), biomarker (i.e. assay), mood-related and cognitive data, using formal tests of association, mediation and moderation. We will use the primary care and HES data in order to ascertain follow-up mood disorders. Our project meets UK Biobank?s stated purpose of improving the prevention, diagnosis and treatment of illnesses by identifying risk factors for lower cognitive ability and mood disorder; important risk factors for physical ill health, earlier mortality and lower quality of life. Insights from this work will lead to a better understanding of disease processes in cognitive decline and Alzheimer's disease (dementia) and mood disorders such as depression, including better approaches to diagnosis and ultimately the development of new treatments. The work will consist of using genome-wide association (GWA) data in the UK Biobank, together with environmental variables e.g. sociodemographics, and lifestyle variables e.g. health related behaviours like smoking status, alcohol intake etc., to test for independent associations with cognitive abilities and mood disorders, both at baseline and at follow-up, based on NHS record linkage. We will test for how these associations are mediated by brain MRI variables, and/or moderated by biomarker variables (e.g. lipid levels, inflammatory markers). The project will make full use of phenotypic, genetic, raw/derived brain MRI/fMRI and biomarker data in the full cohort (as and when each aspect becomes available).
| Lead investigator: | Dr Donald Lyall |
| Lead institution: | University of Glasgow |
6 related Returns
| Return ID | App ID | Description | Archive Date |
|---|---|---|---|
| 3402 | 17689 | Alzheimer's Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769) | 11 May 2021 |
| 2704 | 17689 | Assessing for interaction between APOE e4, sex, and lifestyle on cognitive abilities | 30 Oct 2020 |
| 2728 | 17689 | Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity | 2 Nov 2020 |
| 3403 | 17689 | Association of systolic blood pressure and body mass index with cognitive and structural brain phenotypes in UK Biobank | 11 May 2021 |
| 2729 | 17689 | Social engagement after stroke - is it relevant to cognitive function? A cross-sectional analysis of UK Biobank data | 2 Nov 2020 |
| 2590 | 17689 | The associations between self-reported depression, self-reported chronic inflammatory conditions and cognitive abilities in UK Biobank | 27 Oct 2020 |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 3405 | PCSK9 genetic variants and cognitive abilities: a large-scale Mendelian randomization study | Lyall DM et al. | 2021 | Arch Med Sci |
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