title: Association of AKAP6 and MIR2113 with cognitive performance in a population-based sample of older adults.
abstract: Genetic factors make a substantial contribution to inter-individual variability in cognitive function. A recent meta-analysis of genome-wide association studies identified two loci, AKAP6 and MIR2113, that are associated with general cognitive function. Here, we extend this previous research by investigating the association of MIR2113 and AKAP6 with baseline and longitudinal non-linear change across a broad spectrum of cognitive domains in a community-based cohort of older adults without dementia. Two single nucleotide polymorphisms (SNPs), MIR211-rs10457441 and AKAP6-rs17522122 were genotyped in 1570 non-demented older Australians of European ancestry, who were examined up to 4 times over 12 years. Linear mixed effects models were used to examine the association between AKAP6 and MIR2113 with cognitive performance in episodic memory, working memory, vocabulary, perceptual speed and reaction time at baseline and with linear and quadratic rates of change. AKAP6-rs17522122*T was associated with worse baseline performance in episodic memory, working memory, vocabulary and perceptual speed, but it was not associated with cognitive change in any domain. MIR2113-rs10457441*T was associated with accelerated decline in episodic memory. No other associations with baseline cognitive performance or with linear or quadratic rate or cognitive changes were observed for this SNP. These results confirm the previous finding that AKAP6 is associated with performance across multiple cognitive domains at baseline but not with cognitive decline, while MIR2113 primarily affects the rate at which memory declines over time.
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: S J
authors.identifier: 0000-0002-1921-9470
authors.initials: SJ
authors.lastname: Andrews
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Das
authors.affiliation: Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, Australia.
authors.forename: K J
authors.initials: KJ
authors.lastname: Anstey
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Easteal
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics; D003704:Dementia / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D054758:A Kinase Anchor Proteins; C093173:AKAP6 protein, human; C549405:MIRN211 microRNA, human; D035683:MicroRNAs
keywords: AKAP6; MIR2113; cognition; cognitive decline; population-based cohort; single nucleotide polymorphisms