Polygenic risk for Alzheimer's disease is not associated with cognitive ability or cognitive aging in non-demented older people.
Alzheimer's disease (AD) and non-pathological cognitive aging have phenotypic similarities which may be influenced by an overlapping set of genetic variants. Genome-wide complex trait analysis estimates that common genetic variants account for about 24% of the variation contributing to liability for AD. It is also estimated that 24% of the variance of non-pathological cognitive aging is accounted for by common single nucleotide polymorphisms. However, although the APOE locus is associated with both AD and cognitive aging, it is not known to what extent other common genetic variants, with smaller effect sizes that influence both, overlap. We test the hypothesis that polygenic risk for AD is associated with cognitive ability and cognitive change in about 3,000 non-demented older people (Cognitive Ageing Genetics England and Scotland-CAGES-consortium). We found no significant association of polygenic risk for AD with cognitive ability or cognitive change in CAGES, indicating that the genetic etiologies of AD and non-pathological cognitive decline differ.
Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh, UK Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK.
Sarah E
SE
Harris
Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh, UK Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK Department of Psychology, University of Edinburgh, Edinburgh, UK.
Gail
G
Davies
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK Department of Psychology, University of Edinburgh, Edinburgh, UK.
Michelle
M
Luciano
Centre for Integrated Genomic Medical Research, University of Manchester, Stopford Building, Manchester, UK.
Antony
A
Payton
Institute of Applied Health Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
Helen C
HC
Fox
Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, UK.
Paul
P
Haggarty
Centre for Integrated Genomic Medical Research, University of Manchester, Stopford Building, Manchester, UK.
William
W
Ollier
Centre for Clinical and Cognitive Neuroscience. Institute Brain Behaviour and Mental Health, University of Manchester, Clinical Sciences Building, Salford Royal NHS Foundation Trust, Salford, UK.
Michael
M
Horan
Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh, UK Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK.
David J
DJ
Porteous
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
John M
JM
Starr
Institute of Applied Health Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
Lawrence J
LJ
Whalley
Centre for Clinical and Cognitive Neuroscience. Institute Brain Behaviour and Mental Health, University of Manchester, Clinical Sciences Building, Salford Royal NHS Foundation Trust, Salford, UK.
Neil
N
Pendleton
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK Department of Psychology, University of Edinburgh, Edinburgh, UK.
Ian J
IJ
Deary
D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide
D001057:Apolipoproteins E
Aging; Alzheimer's disease; cognition; cohort studies; genetics; polygenic traits