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

PLoS One. 2018 Jun 1;13(6):e0198187. doi: 10.1371/journal.pone.0198187. eCollection 2018.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / psychology
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Amyotrophic Lateral Sclerosis / psychology
  • Cognition*
  • Forced Expiratory Volume
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / physiopathology
  • Frontotemporal Dementia / psychology
  • Genetic Association Studies
  • Genome-Wide Association Study
  • Humans
  • Mental Status and Dementia Tests
  • Middle Aged
  • Multifactorial Inheritance*
  • Muscle Strength
  • Peak Expiratory Flow Rate
  • Physical Fitness*
  • Risk Assessment
  • United Kingdom