Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease.
Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease.
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DOI：
10.1002/ajmg.b.31053
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发表时间：
2010-06-05
影响因子：
2.8
通讯作者：
Goate, A. M.
中科院分区：
文献类型：
--
作者：
Kauwe, J. S. K.;Bertelsen, S.;Mayo, K.;Cruchaga, C.;Abraham, R.;Hollingworth, P.;Harold, D.;Owen, M. J.;Williams, J.;Lovestone, S.;Morris, J. C.;Goate, A. M.
阿尔茨海默病 (AD) 是一种复杂的疾病，可能受到许多遗传和环境因素的影响。引用铁可能在 AD 病理学中发挥作用的证据，报道血色素沉着症基因 (HFE) 中 rs1049296 (P589S) 和 rs1800562 (C282Y) 之间的上位相互作用导致与 AD 风险显着相关。在这项研究中，我们试图在来自三个欧洲人和欧洲裔美国人的总共 1166 个病例和 1404 个对照中复制他们的发现。三个人群的等位基因和基因型频率是一致的。使用协同因子分析和逻辑回归分析，我们测试了每个群体和组合样本，以了解这两个 SNP 之间的相互作用以及 AD 风险。我们使用协同因子分析（p = 0.0016，协同因子 = 2.71）和根据年龄和 APOE epsilon 4 等位基因的存在进行调整的协同因子分析（p = 0.002，OR = 2.4）观察到组合样本中 rs1049296 和 rs1800562 次要等位基因的双携带者之间存在显着关联。这些结果验证了之前报告的结果，并支持铁转运和调节在 AD 病理学中发挥作用的假设。
Alzheimer's disease (AD) is a complex disease that is likely influenced by many genetic and environmental factors. Citing evidence that iron may play a role in AD pathology, reported that epistatic interaction between rs1049296 (P589S) and rs1800562 (C282Y) in the hemochromatosis gene (HFE) results in significant association with risk for AD. In this study we attempted to replicate their findings in a total of 1166 cases and 1404 controls from three European and European American populations. Allele and genotype frequencies were consistent across the three populations. Using Synergy Factor Analysis and Logistic Regression analysis we tested each population and the combined sample for interactions between these two SNPs and risk for AD. We observed significant association between bi-carriers of the minor alleles of rs1049296 and rs1800562 in the combined sample using Synergy Factor Analysis (p=0.0016, synergy factor=2.71) and adjusted Synergy Factor Analysis adjusting for age and presence of the APOE epsilon 4 allele (p=0.002, OR=2.4). These results validate those of the previous report and support the hypothesis that iron transport and regulation play a role in AD pathology.
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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
影响因子：
--
作者：
Li, Hao;Wetten, Sally;Roses, Allen D.
通讯作者：
Roses, Allen D.
影响因子：
1.8
作者：
Cortina-Borja M;Smith AD;Combarros O;Lehmann DJ
通讯作者：
Lehmann DJ
影响因子：
9.8
作者：
Bertram, Lars;Lange, Christoph;Tanzi, Rudolph E.
通讯作者：
Tanzi, Rudolph E.
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.