Association of genetic risk factors with cognitive decline: the PATH through life project

Shea J Andrews; Debjani Das; Nicolas Cherbuin; Kaarin J Anstey; Simon Easteal

doi:10.1016/j.neurobiolaging.2016.02.016

Association of genetic risk factors with cognitive decline: the PATH through life project

Neurobiol Aging. 2016 May:41:150-158. doi: 10.1016/j.neurobiolaging.2016.02.016. Epub 2016 Feb 21.

Authors

Shea J Andrews¹, Debjani Das², Nicolas Cherbuin³, Kaarin J Anstey³, Simon Easteal²

Affiliations

¹ Department of Genome Sciences, John Curtin School of Medical Research, Australian National University, Canberra, ACT Australia. Electronic address: shea.andrews@anu.edu.au.
² Department of Genome Sciences, John Curtin School of Medical Research, Australian National University, Canberra, ACT Australia.
³ Centre for Research on Ageing, Health & Wellbeing, Research School of Population Health, Australian National University, Canberra, ACT Australia.

PMID: 27103528
DOI: 10.1016/j.neurobiolaging.2016.02.016

Abstract

We examined the association of 28 single nucleotide polymorphisms (SNPs), previously associated with dementia or cognitive performance, with tests assessing episodic memory, working memory, vocabulary, and perceptual speed in 1689 nondemented older Australians of European ancestry. In addition to testing each variant individually, we assessed the collective association of the 12-risk SNPs for late-onset Alzheimer's disease using weighted and unweighted genetic risk scores. Significant associations with cognitive performance were observed for APOE ε4 allele, ABCA7-rs3764650, CR1-rs3818361, MS4A4E-rs6109332, BDNF-rs6265, COMT-rs4680, CTNNBL-rs6125962, FRMD4A-rs17314229, FRMD4A-rs17314229, intergenic SNP chrX-rs12007229, PDE7A-rs10808746, SORL1-rs668387, and ZNF224-rs3746319. In addition, the weighted genetic risk score was associated with worse performance on episodic memory. The identification of genetic risk factors, that act individually or collectively, may help in screening for people with elevated risk of cognitive decline and for understanding the biological pathways that underlie cognitive decline.

Keywords: Alzheimer's disease; Cognitive decline; Genetic risk scores; Population-based study; SNPs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alzheimer Disease / genetics
Alzheimer Disease / psychology
Cognition
Cognitive Dysfunction / genetics*
Cognitive Dysfunction / psychology
Female
Genetic Association Studies*
Humans
Male
Memory, Episodic
Middle Aged
Polymorphism, Single Nucleotide / genetics*
Risk Factors
Young Adult