Association and heterogeneity at the GAPDH locus in Alzheimer's disease

Mariet Allen, Claire Cox, Olivia Belbin, Li Ma, Gina D. Bisceglio, Samantha L. Wilcox, Chanley C. Howell, Talisha A. Hunter, Oliver Culley, Louise P. Walker, Minerva M. Carrasquillo, Dennis W. Dickson, Ronald C. Petersen, Neill R. Graff-Radford, Steven G. Younkin, Nilüfer Ertekin-Taner

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) and its paralogs were implicated in late-onset Alzheimer's disease (LOAD), although the strength and direction of association have not been consistent. We genotyped 3 previously reported single nucleotide polymorphisms (SNPs; rs3741916- GAPDH 5' UTR, rs2029721- pGAPD, and rs4806173- GAPDHS) in 3 case-control series (2112 cases and 3808 controls). Rs3741916 showed the strongest LOAD association (p = 0.003). The minor allele of rs3741916 showed a protective effect in our combined series (odds ratio [OR] = 0.87%, 95% confidence interval [CI] = 0.79-0.96). This is consistent with results from the 2 published follow-up studies and in opposite direction of the original report. Meta-analysis of the published series with ours suggests presence of heterogeneity (Breslow-Day p < 0.0001). Meta-analysis of only the follow-up series including ours revealed a significant protective effect for the minor allele of rs3741916 (OR = 0.85%, 95% CI = 0.76-0.96, p = 0.009). Our results support the presence of LOAD variants and heterogeneity at the GAPDH locus. The most promising rs3741916 variant is unlikely to be functional given opposing effects in different series. Identification of functional variant(s) in this region likely awaits deep sequencing.

Original languageEnglish (US)
Pages (from-to)203.e25-203.e33
JournalNeurobiology of aging
Volume33
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Alzheimer's disease
  • Association studies in genetics
  • Case control studies

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Association and heterogeneity at the GAPDH locus in Alzheimer's disease'. Together they form a unique fingerprint.

  • Cite this