Association of common KIBRA variants with episodic memory and AD risk

Neurobiol Aging. 2011 Mar;32(3):557.e1-9. doi: 10.1016/j.neurobiolaging.2010.11.004. Epub 2010 Dec 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Mental Recall / physiology*
  • Meta-Analysis as Topic
  • Middle Aged
  • Neuropsychological Tests
  • Phosphoproteins
  • Polymorphism, Single Nucleotide / genetics*
  • Proteins / genetics*
  • Risk Factors
  • United States / epidemiology


  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Proteins
  • WWC1 protein, human