Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
复制标题
全基因分析检测到阿尔茨海默氏病的两个新的易感基因。
DOI：
10.1371/journal.pone.0094661
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cardiovascular Health Study (CHS)
中科院分区：
文献类型：
--
作者：
Escott-Price V;Bellenguez C;Wang LS;Choi SH;Harold D;Jones L;Holmans P;Gerrish A;Vedernikov A;Richards A;DeStefano AL;Lambert JC;Ibrahim-Verbaas CA;Naj AC;Sims R;Jun G;Bis JC;Beecham GW;Grenier-Boley B;Russo G;Thornton-Wells TA;Denning N;Smith AV;Chouraki V;Thomas C;Ikram MA;Zelenika D;Vardarajan BN;Kamatani Y;Lin CF;Schmidt H;Kunkle B;Dunstan ML;Vronskaya M;United Kingdom Brain Expression Consortium;Johnson AD;Ruiz A;Bihoreau MT;Reitz C;Pasquier F;Hollingworth P;Hanon O;Fitzpatrick AL;Buxbaum JD;Campion D;Crane PK;Baldwin C;Becker T;Gudnason V;Cruchaga C;Craig D;Amin N;Berr C;Lopez OL;De Jager PL;Deramecourt V;Johnston JA;Evans D;Lovestone S;Letenneur L;Hernández I;Rubinsztein DC;Eiriksdottir G;Sleegers K;Goate AM;Fiévet N;Huentelman MJ;Gill M;Brown K;Kamboh MI;Keller L;Barberger-Gateau P;McGuinness B;Larson EB;Myers AJ;Dufouil C;Todd S;Wallon D;Love S;Rogaeva E;Gallacher J;George-Hyslop PS;Clarimon J;Lleo A;Bayer A;Tsuang DW;Yu L;Tsolaki M;Bossù P;Spalletta G;Proitsi P;Collinge J;Sorbi S;Garcia FS;Fox NC;Hardy J;Naranjo MC;Bosco P;Clarke R;Brayne C;Galimberti D;Scarpini E;Bonuccelli U;Mancuso M;Siciliano G;Moebus S;Mecocci P;Zompo MD;Maier W;Hampel H;Pilotto A;Frank-García A;Panza F;Solfrizzi V;Caffarra P;Nacmias B;Perry W;Mayhaus M;Lannfelt L;Hakonarson H;Pichler S;Carrasquillo MM;Ingelsson M;Beekly D;Alvarez V;Zou F;Valladares O;Younkin SG;Coto E;Hamilton-Nelson KL;Gu W;Razquin C;Pastor P;Mateo I;Owen MJ;Faber KM;Jonsson PV;Combarros O;O'Donovan MC;Cantwell LB;Soininen H;Blacker D;Mead S;Mosley TH Jr;Bennett DA;Harris TB;Fratiglioni L;Holmes C;de Bruijn RF;Passmore P;Montine TJ;Bettens K;Rotter JI;Brice A;Morgan K;Foroud TM;Kukull WA;Hannequin D;Powell JF;Nalls MA;Ritchie K;Lunetta KL;Kauwe JS;Boerwinkle E;Riemenschneider M;Boada M;Hiltunen M;Martin ER;Schmidt R;Rujescu D;Dartigues JF;Mayeux R;Tzourio C;Hofman A;Nöthen MM;Graff C;Psaty BM;Haines JL;Lathrop M;Pericak-Vance MA;Launer LJ;Van Broeckhoven C;Farrer LA;van Duijn CM;Ramirez A;Seshadri S;Schellenberg GD;Amouyel P;Williams J;Cardiovascular Health Study (CHS)
阿尔茨海默病是一种常见的衰弱性痴呆，具有已知的遗传性，已确定了20个迟发性易感基因座，但仍有待发现。这项研究试图使用另一种全基因分析方法来识别新的易感基因，该方法测试基因内的关联模式，在阿尔茨海默病项目国际基因组学联盟的强大全基因组关联数据集中，包括来自25，580名阿尔茨海默病病例和48，466名对照的超过700万种基因型。除了早期报道的基因外，我们还在8号染色体（TP53INP1，p = 1.4 × 10 − 6）和14号染色体（IGHV1 - 67 p = 7.9 × 10 − 8）上检测到了全基因组显著性位点，这些位点指示了新的易感性位点。 在这项研究中发现的其他基因具有一系列先前与阿尔茨海默病有关的功能，包括能量代谢，蛋白质降解和免疫系统方面，并进一步增加了这些途径作为阿尔茨海默病潜在治疗靶点的重要性。
Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci. The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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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：
4.8
作者：
Katz, Chen;Zaltsman-Amir, Yehudit;Friedler, Assaf
通讯作者：
Friedler, Assaf
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
4
作者：
Bénit, P;Slama, A;Rustin, P
通讯作者：
Rustin, P
影响因子：
2.1
作者：
Li, Yun;Willer, Cristen J.;Ding, Jun;Scheet, Paul;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.