Genome-wide association study of Alzheimer's disease.
Genome-wide association study of Alzheimer's disease.
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DOI：
10.1038/tp.2012.45
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发表时间：
2012-05-15
影响因子：
6.8
通讯作者：
Barmada MM
中科院分区：
文献类型：
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作者：
Kamboh MI;Demirci FY;Wang X;Minster RL;Carrasquillo MM;Pankratz VS;Younkin SG;Saykin AJ;Alzheimer's Disease Neuroimaging Initiative;Jun G;Baldwin C;Logue MW;Buros J;Farrer L;Pericak-Vance MA;Haines JL;Sweet RA;Ganguli M;Feingold E;Dekosky ST;Lopez OL;Barmada MM
除了载脂蛋白 E (APOE) 之外，最近的大型全基因组关联研究 (GWAS) 还确定了与迟发性阿尔茨海默病 (LOAD) 相关的其他 9 个基因/位点（CR1、BIN1、CLU、PICALM、MS4A4/MS4A6E、CD2AP、CD33、EPHA1 和 ABCA7）。然而，已知位点的遗传效应约为 50%，这表明 LOAD 的其他风险基因仍有待确定。在这项研究中，我们使用匹兹堡大学的新 GWAS 数据集（1291 例病例和 938 例对照）详细检查了最近与阿尔茨海默病（AD）风险相关的 9 个新区域，并利用 P<0.01 的前 1% GWAS 单核苷酸多态性（SNP）以及四个独立数据集（2727 例病例和 3336 例对照）对这些数据进行了荟萃分析。 SNP 致力于识别新的 AD 位点。新的 GWAS 数据在 Illumina Omni1-Quad 芯片上生成，并根据约 250 万个标记进行估算。正如预期的那样，APOE 区域中的几个标记在匹兹堡样本中显示出全基因组的显着关联。虽然我们观察到五个基因（PICALM、BIN1、ABCA7、MS4A4/MS4A6E 和 EPHA1）内部或邻近的名义显着关联（P<0.05），但在其余四个基因（CD33、CLU、CD2AP 和 CR1）之外 69-180 kb 处观察到显着信号。对前 1% SNP 的荟萃分析揭示了 PPP1R3B 基因中的暗示性新关联（顶部 SNP rs3848140，P=3.05E–07）。该 SNP 与 AD 风险的关联在所有五个样本中都是一致的，荟萃分析优势比为 2.43。这是 AD 的潜在候选基因，因为它在大脑中表达并参与脂质代谢。这些发现需要在额外的样本中得到证实。
In addition to apolipoprotein E (APOE), recent large genome-wide association studies (GWASs) have identified nine other genes/loci (CR1, BIN1, CLU, PICALM, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7) for late-onset Alzheimer's disease (LOAD). However, the genetic effect attributable to known loci is about 50%, indicating that additional risk genes for LOAD remain to be identified. In this study, we have used a new GWAS data set from the University of Pittsburgh (1291 cases and 938 controls) to examine in detail the recently implicated nine new regions with Alzheimer's disease (AD) risk, and also performed a meta-analysis utilizing the top 1% GWAS single-nucleotide polymorphisms (SNPs) with P<0.01 along with four independent data sets (2727 cases and 3336 controls) for these SNPs in an effort to identify new AD loci. The new GWAS data were generated on the Illumina Omni1-Quad chip and imputed at ∼2.5 million markers. As expected, several markers in the APOE regions showed genome-wide significant associations in the Pittsburg sample. While we observed nominal significant associations (P<0.05) either within or adjacent to five genes (PICALM, BIN1, ABCA7, MS4A4/MS4A6E and EPHA1), significant signals were observed 69–180 kb outside of the remaining four genes (CD33, CLU, CD2AP and CR1). Meta-analysis on the top 1% SNPs revealed a suggestive novel association in the PPP1R3B gene (top SNP rs3848140 with P=3.05E–07). The association of this SNP with AD risk was consistent in all five samples with a meta-analysis odds ratio of 2.43. This is a potential candidate gene for AD as this is expressed in the brain and is involved in lipid metabolism. These findings need to be confirmed in additional samples.
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DOI：
10.1161/atvbaha.109.201020
发表时间：
2010-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Waterworth DM;Ricketts SL;Song K;Chen L;Zhao JH;Ripatti S;Aulchenko YS;Zhang W;Yuan X;Lim N;Luan J;Ashford S;Wheeler E;Young EH;Hadley D;Thompson JR;Braund PS;Johnson T;Struchalin M;Surakka I;Luben R;Khaw KT;Rodwell SA;Loos RJ;Boekholdt SM;Inouye M;Deloukas P;Elliott P;Schlessinger D;Sanna S;Scuteri A;Jackson A;Mohlke KL;Tuomilehto J;Roberts R;Stewart A;Kesäniemi YA;Mahley RW;Grundy SM;Wellcome Trust Case Control Consortium;McArdle W;Cardon L;Waeber G;Vollenweider P;Chambers JC;Boehnke M;Abecasis GR;Salomaa V;Järvelin MR;Ruokonen A;Barroso I;Epstein SE;Hakonarson HH;Rader DJ;Reilly MP;Witteman JC;Hall AS;Samani NJ;Strachan DP;Barter P;van Duijn CM;Kooner JS;Peltonen L;Wareham NJ;McPherson R;Mooser V;Sandhu MS
通讯作者：
Sandhu MS
影响因子：
6.1
作者：
Glorioso, Christin;Oh, Sunghee;Douillard, Gaelle Guilloux;Sibille, Etienne
通讯作者：
Sibille, Etienne
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：
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：
64.8
作者：
通讯作者：
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