Association between polygenic risk for Alzheimer’s disease, brain structure and cognitive abilities in UK Biobank

Tank, R., Ward, J. , Flegal, K. E. , Smith, D. J. , Bailey, M. E.S. , Cavanagh, J. and Lyall, D. M. (2021) Association between polygenic risk for Alzheimer’s disease, brain structure and cognitive abilities in UK Biobank. Neuropsychopharmacology, (doi: 10.1038/s41386-021-01190-4) (Early Online Publication)

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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.

Item Type:Articles
Additional Information:Funding: UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council (MRC), Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. RT was funded by Baillie Gifford studentship (Application Ref: 00482282).
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel and Flegal, Dr Kristin and Bailey, Dr Mark and Cavanagh, Professor Jonathan and Ward, Dr Joey and Tank, Rachana and Lyall, Dr Donald
Authors: Tank, R., Ward, J., Flegal, K. E., Smith, D. J., Bailey, M. E.S., Cavanagh, J., and Lyall, D. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Neuropsychopharmacology
Publisher:Springer Nature
ISSN:0893-133X
ISSN (Online):1740-634X
Published Online:07 October 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Neuropsychopharmacology 2021
Publisher Policy:Reproduced under a Creative Commons License
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