title: Association of common KIBRA variants with episodic memory and AD risk.
abstract: KIBRA single nucleotide polymorphism (SNP) rs17070145 was identified in a genome-wide association study (GWAS) of memory performance, with some but not all follow-up studies confirming association of its T allele with enhanced memory. This allele was associated with reduced Alzheimer's disease (AD) risk in 1 study, which also found overexpression of KIBRA in memory-related brain regions of AD. We genotyped rs17070145 and 14 additional SNPs in 2571 late onset Alzheimer's disease (LOAD) patients vs. 2842 controls, including African-Americans. We found significantly reduced risk for rs17070145 T allele in the older African-American subjects (p = 0.007) and a suggestive effect in the older Caucasian series. Meta-analysis of this allele in > 8000 subjects from our and published series showed a suggestive protective effect (p = 0.07). Analysis of episodic memory in control subjects did not identify associations with rs17070145, though other SNPs showed significant associations in 1 series. KIBRA showed evidence of overexpression in the AD temporal cortex (p = 0.06) but not cerebellum. These results suggest a modest role for KIBRA as a cognition and AD risk gene, and also highlight the multifactorial complexity of its genetic associations.
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Burgess
authors.forename: Otto
authors.initials: O
authors.lastname: Pedraza
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Meron
authors.initials: M
authors.lastname: Hirpa
authors.forename: Fanggeng
authors.initials: F
authors.lastname: Zou
authors.forename: Richard
authors.initials: R
authors.lastname: Miles
authors.forename: Thuy
authors.initials: T
authors.lastname: Nguyen
authors.forename: Ma
authors.initials: M
authors.lastname: Li
authors.forename: John A
authors.initials: JA
authors.lastname: Lucas
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ivnik
authors.forename: Julia
authors.initials: J
authors.lastname: Crook
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Steven G
authors.initials: SG
authors.lastname: Younkin
authors.forename: Nilüfer
authors.initials: N
authors.lastname: Ertekin-Taner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009483:Neuropsychological Tests; D010750:Phosphoproteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; C513637:WWC1 protein, human