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

By Saskia P Hagenaars, Ratko Radakovic, Christopher Crockford, Chloe Fawns-Ritchie, International FTD-Genomics Consortium (IFGC), Sarah E. Harris, Catharine Gale, Ian J Deary

Posted 14 Nov 2017
bioRxiv DOI: 10.1101/219345 (published DOI: 10.1371/journal.pone.0198187)

INTRODUCTION: It is unclear whether polygenic risk for neurodegenerative disease is associated with cognitive performance and physical health. METHODS: This study tested whether polygenic scores for Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) are associated with cognitive performance and physical health. Group-based analyses were performed to compare associations with cognitive and physical function outcomes in the top and bottom 10% for the three neurodegenerative polygenic risk scores. RESULTS: Higher polygenic risk scores for AD, ALS, and FTD were associated with lower cognitive performance. Higher polygenic risk scores 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. DISCUSSION: Our results suggest overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health.

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