Association of genetic risk factors with cognitive decline: the PATH through life project.
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.
Department of Genome Sciences, John Curtin School of Medical Research, Australian National University, Canberra, ACT Australia. Electronic address: shea.andrews@anu.edu.au.
Shea J
SJ
Andrews
Department of Genome Sciences, John Curtin School of Medical Research, Australian National University, Canberra, ACT Australia.
Debjani
D
Das
Centre for Research on Ageing, Health & Wellbeing, Research School of Population Health, Australian National University, Canberra, ACT Australia.
Nicolas
N
Cherbuin
Centre for Research on Ageing, Health & Wellbeing, Research School of Population Health, Australian National University, Canberra, ACT Australia.
Kaarin J
KJ
Anstey
Department of Genome Sciences, John Curtin School of Medical Research, Australian National University, Canberra, ACT Australia.
Simon
S
Easteal
D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics / Q000523:psychology; D003071:Cognition; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000523:psychology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
Alzheimer's disease; Cognitive decline; Genetic risk scores; Population-based study; SNPs