Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these groups were compared on the cognitive and physical health variables. Higher polygenic risk for AD, ALS, and FTD was associated with lower cognitive performance. Higher polygenic risk for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS. The results suggest some overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health

Associations between polygenic risk scores for Alzheimer’s disease (FDR p-value ≤ 0.018), amyotrophic lateral sclerosis (FDR p-value ≤ 0.0024), and frontotemporal dementia (FDR p-value ≤ 0.0041), and cognitive and physical measures controlling for age, sex, assessment centre, genotyping batch and array and 10 genetic principal components for population structure.

<p>Associations between polygenic risk scores for Alzheimer’s disease (FDR p-value ≤ 0.018), amyotrophic lateral sclerosis (FDR p-value ≤ 0.0024), and frontotemporal dementia (FDR p-value ≤ 0.0041), and cognitive and physical measures controlling for age, sex, assessment centre, genotyping batch and array and 10 genetic principal components for population structure.</p

Heat map of associations between the polygenic profile scores for neurodegenerative disease and cognitive ability and physical health.

<p>Stronger associations are indicated by darker shades, red indicates a positive association, blue indicates a negative association. AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia; TMT B-A, trail-making part B–part A; TMT B, trail making part B; TMT A, trail making part A; DSS, digit symbol substitution; VNR, verbal numerical reasoning; FVC, forced vital capacity; PEF, peak expiratory flow; FEV1, forced expiratory volume in 1s. *, significant association after FDR correction (p-value ≤ 0.018 (AD), 0.024 (ALS), or 0.0041 (FTD)). Full results can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198187#pone.0198187.s001" target="_blank">S1 Table</a>.</p

Cognitive and physical variable comparison between high Alzheimer’s disease (AD) polygenic risk, amyotrophic lateral sclerosis (ALS) polygenic risk, and frontotemporal dementia (FTD) polygenic risk, N for each group is shown.

<p>Cognitive and physical variable comparison between high Alzheimer’s disease (AD) polygenic risk, amyotrophic lateral sclerosis (ALS) polygenic risk, and frontotemporal dementia (FTD) polygenic risk, N for each group is shown.</p