Association of common KIBRA variants with episodic memory and AD risk

Jeremy D. Burgess, Otto D Pedraza, Neill R Graff Radford, Meron Hirpa, Fanggeng Zou, Richard Miles, Thuy Nguyen, Ma Li, John A Lucas, Robert J. Ivnik, Juliana Crook, V. Shane Pankratz, Dennis W Dickson, Ronald Carl Petersen, Steven G Younkin, Nilufer Taner

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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.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume32
Issue number3
DOIs
StatePublished - Mar 2011

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Keywords

  • Alzheimer's disease
  • Association studies in genetics
  • Case control studies
  • Episodic memory
  • Gene expression
  • KIBRA

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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