Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.
Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.
复制标题
DOI：
10.1038/ng.440
复制
发表时间：
2009-10
期刊：
影响因子：
30.8
通讯作者：
Williams, Julie
中科院分区：
文献类型：
--
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
我们进行了一项两阶段的阿尔茨海默病全基因组关联研究，涉及16，000多人。在阶段1中（3，941例病例和7，848例对照），我们复制了与APOE基因座的既定关联，（最显著的SNP：rs 2075650，p= 1.8×10−157），并观察到与两个新基因座的SNP的全基因组显著关联：CLU或APOJ基因中的rs 11136000（p= 1.4×10−9）和PICALM基因5′端的SNP rs3851179（p= 1.9×10−8）。这两种新的关联在第2阶段（2,023例病例和2,340例对照）得到了支持，在联合数据集中产生了与AD相关的令人信服的证据（rs 11136000：p= 8.5×10−10，比值比= 0.86; rs3851179：p= 1.3×10−9，比值比= 0.86）。我们还观察到p< 1×10 - 5的相关变异比偶然预期的要多（p=7.5×10 - 6），包括BIN 1、DAB 1和CR 1基因座的多态性。
We undertook a two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the APOE locus (most significant SNP: rs2075650, p= 1.8×10−157) and observed genome-wide significant association with SNPs at two novel loci: rs11136000 in the CLU or APOJ gene (p= 1.4×10−9) and rs3851179, a SNP 5′ to the PICALM gene (p= 1.9×10−8). Both novel associations were supported in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with AD in the combined dataset (rs11136000: p= 8.5×10−10, odds ratio= 0.86; rs3851179: p= 1.3×10−9, odds ratio= 0.86). We also observed more variants associated at p< 1×10−5 than expected by chance (p=7.5×10−6), including polymorphisms at the BIN1, DAB1 and CR1 loci.
登录
查看更多内容
影响因子：
12.3
作者：
Avramopoulos D
通讯作者：
Avramopoulos D
DOI：
10.1073/pnas.93.10.4804
发表时间：
1996-05-14
影响因子：
11.1
作者：
Dreyling, MH;MartinezCliment, JA;Bohlander, SK
通讯作者：
Bohlander, SK
影响因子：
2.7
作者：
Abraham R;Moskvina V;Sims R;Hollingworth P;Morgan A;Georgieva L;Dowzell K;Cichon S;Hillmer AM;O'Donovan MC;Williams J;Owen MJ;Kirov G
通讯作者：
Kirov G
影响因子：
5.3
作者：
Fitzjohn, SM;Morton, RA;Seabrook, GR
通讯作者：
Seabrook, GR
影响因子：
30.8
作者：
Clayton, DG;Walker, NM;Todd, JA
通讯作者：
Todd, JA