Association of common KIBRA variants with episodic memory and AD risk

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

Research output: Contribution to journalArticle

36 Scopus citations

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)
Pages (from-to)557.e1-557.e9
JournalNeurobiology of aging
Volume32
Issue number3
DOIs
StatePublished - Mar 2011

Keywords

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

ASJC Scopus subject areas

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

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