The effects of the TOMM40 poly-T alleles on Alzheimer's disease phenotypes.
The effects of the TOMM40 poly-T alleles on Alzheimer's disease phenotypes.
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DOI：
10.1016/j.jalz.2018.01.015
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Lutz MW
中科院分区：
文献类型：
--
作者：
Chiba-Falek O;Gottschalk WK;Lutz MW
TOMM40 poly-T是TOMM40基因6内含子的多态性，它与APOE的LD相邻且在LD中。Roses及其同事发现了TOMM40 poly-T的长度与晚发型阿尔茨海默病（LOAD）发病风险和年龄之间的关系。在最初的发现之后，其他研究发现TOMM40 poly-T和load相关表型之间存在独立于APOE基因型的关联，而其他研究则没有重复这些关联。此外，在不同的负载相关表型之间，TOMM40多t风险等位基因的身份一直存在争议。在这里，我们提出了一个框架来解决关于与load表型及其功能影响相关的TOMM40多t等位基因的矛盾发现。该框架用于解释先前的研究，以获得有关风险等位基因VL与s的性质的见解。我们建议TOMM40多t风险等位基因的身份取决于被评估的表型，评估时研究对象的年龄以及APOE基因型的背景。在结束语中，我们概述了未来的研究，将告知遗传数据的机制解释。
The TOMM40 poly-T is a polymorphism in intron 6 of the TOMM40 gene, which is adjacent to and in LD with APOE. Roses and colleagues identified the association between the length of TOMM40 poly-T with the risk and age of onset of late-onset Alzheimer’s disease (LOAD). Following the original discovery, additional studies found associations between the TOMM40 poly-T and LOAD-related phenotypes independent of APOE genotypes, while others did not replicate these associations. Furthermore, the identity of the TOMM40 poly-T risk allele has been controversial between different LOAD-related phenotypes. Here we propose a framework to address the conflicting findings with respect to the TOMM40 poly-T alleles associations with LOAD-phenotypes and its functional effects. The framework is used to interpret previous studies as means to gain insights regarding the nature of the risk allele, VL vs. S. We suggest that the identity of the TOMM40 poly-T risk allele depends on the phenotype being evaluated, the ages of the study subjects at the time of assessment, and the context of the APOE genotypes. In concluding remarks we outline future studies that will inform the mechanistic interpretation of the genetic data.
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DOI：
10.1016/j.jalz.2016.12.009
发表时间：
2017-07
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Burggren AC;Mahmood Z;Harrison TM;Siddarth P;Miller KJ;Small GW;Merrill DA;Bookheimer SY
通讯作者：
Bookheimer SY
影响因子：
3.7
作者：
Bruno, Davide;Nierenberg, Jay J.;Ritchie, James C.;Lutz, Michael W.;Pomara, Nunzio
通讯作者：
Pomara, Nunzio
APOE 位点遗传变异的功能分析表明区域增强子参与 TOMM40 和 APOE 的调节。
影响因子：
3.5
作者：
通讯作者：
--
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：
Cruchaga, Carlos;Nowotny, Petra;Goate, Alison M.
通讯作者：
Goate, Alison M.