| Title: | Association between polygenic risk for Alzheimer's disease, brain structure and cognitive abilities in UK Biobank |
| Journal: | Neuropsychopharmacology |
| Published: | 7 Oct 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34621014/ |
| DOI: | https://doi.org/10.1038/s41386-021-01190-4 |
| URL: | https://www.nature.com/articles/s41386-021-01190-4.pdf |
| Citations: | 20 (8 in last 2 years) as of 8 Aug 2024 |
Publication 4158
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Abstract
Previous studies testing associations between polygenic risk for late-onset Alzheimer's disease (LOAD-PGR) and brain magnetic resonance imaging (MRI) measures have been limited by small samples and inconsistent consideration of potential confounders. This study investigates whether higher LOAD-PGR is associated with differences in structural brain imaging and cognitive values in a relatively large sample of non-demented, generally healthy adults (UK Biobank). Summary statistics were used to create PGR scores for n = 32,790 participants using LDpred. Outcomes included 12 structural MRI volumes and 6 concurrent cognitive measures. Models were adjusted for age, sex, body mass index, genotyping chip, 8 genetic principal components, lifetime smoking, apolipoprotein (APOE) e4 genotype and socioeconomic deprivation. We tested for statistical interactions between APOE e4 allele dose and LOAD-PGR vs. all outcomes. In fully adjusted models, LOAD-PGR was associated with worse fluid intelligence (standardised beta [β] = −0.080 per LOAD-PGR standard deviation, p = 0.002), matrix completion (β = −0.102, p = 0.003), smaller left hippocampal total (β = −0.118, p = 0.002) and body (β = −0.069, p = 0.002) volumes, but not other hippocampal subdivisions. There were no significant APOE x LOAD-PGR score interactions for any outcomes in fully adjusted models. This is the largest study to date investigating LOAD-PGR and non-demented structural brain MRI and cognition phenotypes. LOAD-PGR was associated with smaller hippocampal volumes and aspects of cognitive ability in healthy adults and could supplement APOE status in risk stratification of cognitive impairment/LOAD.</p>
7 Authors
- Rachana Tank
- Joey Ward
- Kristin E. Flegal
- Daniel J. Smith
- Mark E. S. Bailey
- Jonathan Cavanagh
- Donald M. Lyall
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