@article{7d7d0eec3d474ed584d8ef560c64b45f,
title = "Association and heterogeneity at the GAPDH locus in Alzheimer's disease",
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.",
keywords = "Alzheimer's disease, Association studies in genetics, Case control studies",
author = "Mariet Allen and Claire Cox and Olivia Belbin and Li Ma and Bisceglio, {Gina D.} and Wilcox, {Samantha L.} and Howell, {Chanley C.} and Hunter, {Talisha A.} and Oliver Culley and Walker, {Louise P.} and Carrasquillo, {Minerva M.} and Dickson, {Dennis W.} and Petersen, {Ronald C.} and Graff-Radford, {Neill R.} and Younkin, {Steven G.} and Nil{\"u}fer Ertekin-Taner",
note = "Funding Information: Support for this research was provided by the National Institutes of Health grants: National Institute on Aging , R01 AG018023 to NRG-R and SGY; Mayo Alzheimer's Disease Research Center , P50 AG016574 to RCP, DWD, NRG-R, and SGY; Mayo Alzheimer's Disease Patient Registry , U01 AG006576 to RCP; and National Institute on Aging , AG025711 , AG017216 , and AG003949 to DWD. This project was also generously supported by the Robert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program (to RCP, DWD, NRG-R, SGY) and by the Palumbo Professorship in Alzheimer's Disease Research (to SGY). NE-T is the recipient of National Institute on Aging ( F32 AG20903 ), National Institutes of Health ( KL2 RR024151 ), Johnnie B. Byrd , and Siragusa Foundation grants. OB thanks the Alzheimer's Research Trust (ART) for funding. Funding Information: R.C. Petersen, MD, PhD has been a consultant to GE Healthcare and Elan Pharmaceuticals, has served on a data safety monitoring board in a clinical trial sponsored by Elan Pharmaceuticals, and a safety monitoring board for Wyeth Pharmaceuticals. N. Graff-Radford, MD has served as a consultant to Codman and received grant support from Elan Pharmaceutical Research, Pfizer Pharmaceuticals, Medivation, and Forrest. The remaining authors report no disclosures. ",
year = "2012",
month = jan,
doi = "10.1016/j.neurobiolaging.2010.08.002",
language = "English (US)",
volume = "33",
pages = "203.e25--203.e33",
journal = "Neurobiology of aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "1",
}