Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
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我们试图通过阶段性关联研究（GERAD+）和阿尔茨海默病遗传联盟（ADGC）报告的提示性基因座检测来确定阿尔茨海默病（AD）的新易感基因座。首先，我们对四个全基因组关联数据集进行了综合分析（第一阶段），并确定了10个P≤1×10−5的新变体。在一个独立的样本中检测这些数据的相关性（第2阶段）。在两个基因座的三个SNP复制，并在进一步的样品中显示出关联的证据（阶段3）。所有数据的荟萃分析提供了令人信服的证据，表明ABCA 7（meta-P 4.5×10−17;包括ADGC meta-P =5.0×10−21）和MS 4A基因簇（rs610932，meta-P =1.8×10−14;包括ADGC meta-P =1.2×10−16; rs670139，meta-P =1.4×10−9;包括ADGC meta-P =1.1×10−10）是AD的新易感基因座。其次，我们观察到ADGC GWAS报告的三个提示性位点相关的独立证据，当它们组合在一起时显示出全基因组意义：（GERAD+ P=8.0×10−4;包括ADGC meta-P =8.6×10−9），CD 33（GERAD+ P=2.2×10−4;包括ADGC meta-P =1.6×10−9）和EPHA 1（GERAD+ P=3.4×10−4;包括ADGC meta-P =6.0×10−10）。这些发现支持了5个新的AD易感基因。
We sought to identify new susceptibility loci for Alzheimer’s disease (AD) through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer’s Disease Genetic Consortium (ADGC). First, we undertook a combined analysis of four genome-wide association datasets (Stage 1) and identified 10 novel variants with P≤1×10−5. These were tested for association in an independent sample (Stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (Stage 3). Meta-analyses of all data provide compelling evidence that ABCA7 (meta-P 4.5×10−17; including ADGC meta-P=5.0×10−21) and the MS4A gene cluster (rs610932, meta-P=1.8×10−14; including ADGC meta-P=1.2×10−16; rs670139, meta-P=1.4×10−9; including ADGC meta-P=1.1×10−10) are novel susceptibility loci for AD. Second, we observed independent evidence for association for three suggestive loci reported by the ADGC GWAS, which when combined shows genome-wide significance: CD2AP (GERAD+ P=8.0×10−4; including ADGC meta-P=8.6×10−9), CD33 (GERAD+ P=2.2×10−4; including ADGC meta-P=1.6×10−9) and EPHA1 (GERAD+ P=3.4×10−4; including ADGC meta-P=6.0×10−10). These findings support five novel susceptibility genes for AD.
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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：
Kim, WS;Fitzgerald, ML;Freeman, MW
通讯作者：
Freeman, MW
影响因子：
1.5
作者：
Duffy, Shannon L.;Coulthard, Mark G.;Boyd, Andrew W.
通讯作者：
Boyd, Andrew W.
影响因子：
64.5
作者：
Dustin, ML;Olszowy, MW;Shaw, AS
通讯作者：
Shaw, AS
影响因子：
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作者：
Biffi, Alessandro;Anderson, Christopher D.;Desikan, Rahul S.;Sabuncu, Mert;Cortellini, Lynelle;Schmansky, Nick;Salat, David;Rosand, Jonathan
通讯作者：
Rosand, Jonathan