Polygenic risk for Alzheimer's disease is not associated with cognitive ability or cognitive aging in non-demented older people

Sarah E Harris, Gail Davies, Michelle Luciano, Antony Payton, Helen C Fox, Paul Haggarty, William Ollier, Michael Horan, David J Porteous, John M Starr, Lawrence J Whalley, Neil Pendleton, Ian J Deary

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34 Citations (Scopus)
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Abstract

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.
Original languageEnglish
Pages (from-to)565-574
Number of pages10
JournalJournal of Alzheimer's Disease
Volume39
Issue number3
Early online date18 Nov 2013
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • aging
  • Alzheimer's disease
  • cognition
  • cohort studies
  • genetics
  • polygenic traits

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