Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies.
Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies.
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DOI：
10.1093/hmg/ddu334
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发表时间：
2014-12-01
影响因子：
3.5
通讯作者：
Hardy J
中科院分区：
文献类型：
--
作者：
Bras J;Guerreiro R;Darwent L;Parkkinen L;Ansorge O;Escott-Price V;Hernandez DG;Nalls MA;Clark LN;Honig LS;Marder K;Van Der Flier WM;Lemstra A;Scheltens P;Rogaeva E;St George-Hyslop P;Londos E;Zetterberg H;Ortega-Cubero S;Pastor P;Ferman TJ;Graff-Radford NR;Ross OA;Barber I;Braae A;Brown K;Morgan K;Maetzler W;Berg D;Troakes C;Al-Sarraj S;Lashley T;Compta Y;Revesz T;Lees A;Cairns N;Halliday GM;Mann D;Pickering-Brown S;Dickson DW;Singleton A;Hardy J
路易体痴呆（DLB）、帕金森病和阿尔茨海默病（分别为PD和AD）之间的临床和神经病理学相似性表明，这些疾病可能有共同的病因。为了验证这一假设，我们在一个大的DLB病例和对照组中对先前与PD或AD有关的54个基因组区域进行了关联研究。该队列包括788例DLB病例和2624例对照。为了尽量减少潜在的误诊问题，我们还进行了分析，仅包括神经病理学证实的DLB病例（667例）。结果表明，APOE是DLB的一个强遗传风险因素，证实了以前的研究结果，并且SNCA和SCARB 2基因座在研究Bonferroni校正后也相关，尽管这些与PD中相同基因座报告的相关性不同。我们先前已经表明GBA中的p.N370S变体与DLB相关，这与SCARB2位点的发现一起表明溶酶体功能障碍在这种疾病中的作用。这些结果表明，DLB有一个独特的遗传风险相比，两个最常见的神经退行性疾病，溶酶体可能在这种疾病的病因学中发挥重要作用。我们提供所有这些数据。
Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.
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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：
12.7
作者：
Halliday, Glenda;Hely, Mariese;Morris, John
通讯作者：
Morris, John
影响因子：
29
作者：
Nalls, Michael A.;Duran, Raquel;Sidransky, Ellen
通讯作者：
Sidransky, Ellen
影响因子：
10.5
作者：
McKeith, IG
通讯作者：
McKeith, IG
DOI：
10.1056/nejmoa0901281
发表时间：
2009-10-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sidransky E;Nalls MA;Aasly JO;Aharon-Peretz J;Annesi G;Barbosa ER;Bar-Shira A;Berg D;Bras J;Brice A;Chen CM;Clark LN;Condroyer C;De Marco EV;Dürr A;Eblan MJ;Fahn S;Farrer MJ;Fung HC;Gan-Or Z;Gasser T;Gershoni-Baruch R;Giladi N;Griffith A;Gurevich T;Januario C;Kropp P;Lang AE;Lee-Chen GJ;Lesage S;Marder K;Mata IF;Mirelman A;Mitsui J;Mizuta I;Nicoletti G;Oliveira C;Ottman R;Orr-Urtreger A;Pereira LV;Quattrone A;Rogaeva E;Rolfs A;Rosenbaum H;Rozenberg R;Samii A;Samaddar T;Schulte C;Sharma M;Singleton A;Spitz M;Tan EK;Tayebi N;Toda T;Troiano AR;Tsuji S;Wittstock M;Wolfsberg TG;Wu YR;Zabetian CP;Zhao Y;Ziegler SG
通讯作者：
Ziegler SG