Association and heterogeneity at the GAPDH locus in Alzheimer's disease.
Association and heterogeneity at the GAPDH locus in Alzheimer's disease.
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DOI：
10.1016/j.neurobiolaging.2010.08.002
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发表时间：
2012-01
影响因子：
4.2
通讯作者：
Ertekin-Taner N
中科院分区：
文献类型：
--
作者：
Allen M;Cox C;Belbin O;Ma L;Bisceglio GD;Wilcox SL;Howell CC;Hunter TA;Culley O;Walker LP;Carrasquillo MM;Dickson DW;Petersen RC;Graff-Radford NR;Younkin SG;Ertekin-Taner N
甘油醛-3-磷酸脱氢酶基因（GAPDH）及其类似物与晚发性阿尔茨海默病（LOAD）有关，尽管其关联的强度和方向尚不一致。我们在三个病例对照系列（2112例和3808例对照）中对三个先前报道的snp （rs374196 - gapdh 5'UTR， rs2029721-pGAPD和rs4806173-GAPDHS）进行了基因分型。Rs3741916的LOAD相关性最强（p=0.003）。rs3741916的次要等位基因在我们的联合序列中显示出保护作用（OR=0.87, 95%可信区间(CI)=0.79 ~ 0.96）。这与两项已发表的后续研究的结果一致，与原始报告的方向相反。对已发表的研究进行荟萃分析表明存在异质性（Breslow-Day p<0.0001）。荟萃分析显示rs3741916的次要等位基因具有显著的保护作用（OR=0.85, 95% CI= 0.76-0.96, p=0.009）。我们的研究结果支持在GAPDH位点存在LOAD变异和异质性。考虑到不同系列的相反效应，最有希望的rs3741916变体不太可能起作用。该区域功能变异的鉴定可能有待于深度测序。
Glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) and its paralogues were implicated in late-onset Alzheimer’s disease (LOAD), although the strength and direction of association have not been consistent. We genotyped three previously reported SNPs (rs3741916-GAPDH 5’UTR, rs2029721-pGAPD and rs4806173-GAPDHS) in three 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 (OR=0.87, 95% confidence interval (CI)=0.79–0.96). This is consistent with results from the two 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.
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影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
DOI：
10.1073/pnas.0403535101
发表时间：
2004-11-02
影响因子：
11.1
作者：
Li, Y;Nowotny, P;Grupe, A
通讯作者：
Grupe, A
影响因子：
120.7
作者：
Rogaeva, E;Premkumar, S;St George-Hyslop, PH
通讯作者：
St George-Hyslop, PH
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N
影响因子：
30.8
作者：
Carrasquillo, Minerva M.;Zou, Fanggeng;Pankratz, V. Shane;Wilcox, Samantha L.;Ma, Li;Walker, Louise P.;Younkin, Samuel G.;Younkin, Curtis S.;Younkin, Linda H.;Bisceglio, Gina D.;Ertekin-Taner, Nilufer;Crook, Julia E.;Dickson, Dennis W.;Petersen, Ronald C.;Graff-Radford, Neill R.;Younkin, Steven G.
通讯作者：
Younkin, Steven G.