Younkin, Steven G

Publication Detail

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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; et al. (Profiled Author: Younkin, Steven G)

Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA.
Neurobiology of aging 2012;33(1):203.e25-33.

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.

5 Originating Grant

• 1.

  YOUNKIN, STEVEN G

  Plasma AB as a Surrogate Genetic Marker for LOAD

  1 April 2000 - 31 May 2013

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 3,283,760

• 2.

  Hutton, Michael L

  Tau and Neurodegeneration II: A therapeutic target

  1 September 1999 - 31 May 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 8,997,034

• 3.

  Dickson, Dennis William

  Tau and Neurodegeneration II: A therapeutic target

  1 September 1999 - 31 May 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 4,182,608

• 4.

  PETERSEN, RONALD C

  Mayo Alzheimer's Disease Research Center

  1 May 1999 - 30 April 2014

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 25,743,859

• 5.

  KATZMAN, ROBERT

  TEACHING NURSING HOME

  29 September 1982 - 31 August 1987

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 1,614,817

Scientific Context

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