Genetic variation and neuroimaging measures in Alzheimer disease.
Genetic variation and neuroimaging measures in Alzheimer disease.
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DOI：
10.1001/archneurol.2010.108
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发表时间：
2010-06
影响因子：
--
通讯作者：
Rosand, Jonathan
中科院分区：
文献类型：
--
作者：
Biffi, Alessandro;Anderson, Christopher D.;Desikan, Rahul S.;Sabuncu, Mert;Cortellini, Lynelle;Schmansky, Nick;Salat, David;Rosand, Jonathan
研究全基因组关联研究（GWAS）验证和GWAS有前途的候选位点是否影响磁共振成像测量和临床阿尔茨海默病（AD）状态。来自阿尔茨海默病神经影像学倡议的遗传和神经影像学数据的多中心病例对照研究。多中心GWAS。共有168名可能患有AD的个体，357名轻度认知障碍的个体和215名认知正常的对照个体从美国和加拿大的50多个阿尔茨海默病神经影像学倡议中心招募。所有研究参与者都有APOE和全基因组遗传数据。我们研究了GWAS验证和GWAS有前途的新AD位点对海马体积、杏仁核体积、白色病变体积、内嗅皮质厚度、海马旁回厚度和颞极皮质厚度的影响。APOE位点的标记物与除白色病变体积外的所有表型相关（所有错误发现率校正的P值<0.001）。通过先前的GWAS鉴定的新的和已建立的AD基因座在所有分析的神经影像学指标上显示出显著的累积评分效应（错误发现率P= 0.04）。CR1和PICALM基因座的GWAS验证变异体和2个新基因座的标记物（BIN1和CNTN 5）显示与多种磁共振成像特征相关（错误发现率P <0.05）。与AD相关的基因座也影响这种疾病的神经影像学相关性。此外，神经影像学分析确定了2个额外的高度关注的位点，以供进一步研究。
To investigate whether genome-wide association study (GWAS)–validated and GWAS-promising candidate loci influence magnetic resonance imaging measures and clinical Alzheimer’s disease (AD) status. Multicenter case-control study of genetic and neuroimaging data from the Alzheimer’s Disease Neuroimaging Initiative. Multicenter GWAS. A total of 168 individuals with probable AD, 357 with mild cognitive impairment, and 215 cognitively normal control individuals recruited from more than 50 Alzheimer’s Disease Neuroimaging Initiative centers in the United States and Canada. All study participants had APOE and genome-wide genetic data available. We investigated the influence of GWAS-validated and GWAS-promising novel AD loci on hippocampal volume, amygdala volume, white matter lesion volume, entorhinal cortex thickness, parahippocampal gyrus thickness, and temporal pole cortex thickness. Markers at the APOE locus were associated with all phenotypes except white matter lesion volume (all false discovery rate–corrected P values < .001). Novel and established AD loci identified by prior GWASs showed a significant cumulative score–based effect (false discovery rate P=.04) on all analyzed neuroimaging measures. The GWAS-validated variants at the CR1 and PICALM loci and markers at 2 novel loci (BIN1 and CNTN5) showed association with multiple magnetic resonance imaging characteristics (false discovery rate P <.05). Loci associated with AD also influence neuroimaging correlates of this disease. Furthermore, neuroimaging analysis identified 2 additional loci of high interest for further study.
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影响因子：
16.2
作者：
Kim, Jungsu;Basak, Jacob M.;Holtzman, David M.
通讯作者：
Holtzman, David M.
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：
30.8
作者：
Kathiresan S;Willer CJ;Peloso GM;Demissie S;Musunuru K;Schadt EE;Kaplan L;Bennett D;Li Y;Tanaka T;Voight BF;Bonnycastle LL;Jackson AU;Crawford G;Surti A;Guiducci C;Burtt NP;Parish S;Clarke R;Zelenika D;Kubalanza KA;Morken MA;Scott LJ;Stringham HM;Galan P;Swift AJ;Kuusisto J;Bergman RN;Sundvall J;Laakso M;Ferrucci L;Scheet P;Sanna S;Uda M;Yang Q;Lunetta KL;Dupuis J;de Bakker PI;O'Donnell CJ;Chambers JC;Kooner JS;Hercberg S;Meneton P;Lakatta EG;Scuteri A;Schlessinger D;Tuomilehto J;Collins FS;Groop L;Altshuler D;Collins R;Lathrop GM;Melander O;Salomaa V;Peltonen L;Orho-Melander M;Ordovas JM;Boehnke M;Abecasis GR;Mohlke KL;Cupples LA
通讯作者：
Cupples LA
DOI：
10.3174/ajnr.a1397
发表时间：
2009-03
期刊：
AJNR. American journal of neuroradiology
影响因子：
--
作者：
Desikan RS;Cabral HJ;Fischl B;Guttmann CR;Blacker D;Hyman BT;Albert MS;Killiany RJ
通讯作者：
Killiany RJ
影响因子：
5.7
作者：
Dale, AM;Fischl, B;Sereno, MI
通讯作者：
Sereno, MI