% 0期刊文章%一个Mariet艾伦麦克拉Kachadoorian % % Aditya Karhade %一个莱斯特的邹Fanggeng % %柯蒂斯Younkin高Seng柴% %一个茱莉亚骗子%弗农Pankratz说道%密涅瓦Carrasquillo % Asha Nair %苏米特Middha %一个Sooraj Maharjan % Thuy阮%一个李马%一个金伯利Malphrus %莎拉·林肯%吉娜Bisceglio %一个金Jen克里斯托弗•科尔伯特% %罗纳德·彼得森%一个史蒂文Younkin尼尔Graff-Radford % %一个丹尼斯·迪克森% Nilufer tan % T调查老年痴呆症风险位点的转录调控。(S28.006) % D J神经病学20首页14% % P S28.006 % V 82% N 10补充% X目的:探讨晚发性阿尔茨海默氏症(负载)转录调控GWAS风险位点基因在人类的大脑。背景:我们之前确定的遗传关联的大脑GWAS风险负载水平的基因位点ABCA7, BIN1, CLU, CR1和MS4A4A cisSNPs,包括一些高级广告风险变异。最近,11个额外风险位点被确定通过多个负载GWAS的大荟萃分析。在这项研究中,我们的第一个目标是研究大脑的这些协会11小说负载与cisSNPs位点基因风险。我们的第二个目标是评估可变剪接的潜在作用在这些基因表达关联。设计/方法:我们已经获得的基因表达的措施~ 24000记录在两个脑区(颞叶皮层和小脑)200 ~ 200年的广告主题和~科目使用Illumina公司与其他病理WG-DASL化验。负载GWAS 11将小说位点分析的单核苷酸多态性与相应基因的表达水平在cis,使用线性回归调整适当的协变量。评估可变剪接,我们将使用NanoString nCounter™技术来测量所有已知的候选基因的转录水平在所有负载GWAS位点在大脑~ 350 RNA样本。结果:之前我们已经证明了这种方法的实用程序和预测存在额外的负载基因,大脑同样受到snp的水平。 We postulate that some of these SNPs also confer LOAD risk and some of the expression associations are due to alternative splicing of exons. CONCLUSIONS:Many genes at the LOAD GWAS loci associate with cisSNPs, some of which are the top LOAD risk SNPs. This suggests that many LOAD GWAS variants confer risk by transcriptional regulation of genes at these loci. Dissection of this transcriptional regulation is expected to have implications in the understanding of LOAD pathophysiology. Study Supported by: R01 AG032990, P50 AG016574Disclosure: Dr. Kachadoorian has nothing to disclose. Dr. Allen has nothing to disclose. Dr. Karhade has nothing to disclose. Dr. Karhade has nothing to disclose. Dr. Zou has nothing to disclose. Dr. Chai has nothing to disclose. Dr. Younkin has nothing to disclose. Dr. Crook has nothing to disclose. Dr. Pankratz has received research support from Abbott Laboratories, Inc. Dr. Carrasquillo has nothing to disclose. Dr. Nair has nothing to disclose. Dr. Middha has nothing to disclose. Dr. Maharjan has nothing to disclose. Dr. Nguyen has nothing to disclose. Dr. Ma has nothing to disclose. Dr. Malphrus has nothing to disclose. Dr. Lincoln has nothing to disclose. Dr. Bisceglio has nothing to disclose. Dr. Kolbert has nothing to disclose. Dr. Jen has nothing to disclose. Dr. Petersen has received personal compensation for activities with Pfizer, Inc., and Janssen Alzheimer's Immunotherapy. Dr. Petersen has received royalty payments from Oxford University Press. Dr. Graff-Radford has received personal compensation for activities with Codman as a member of a scientific advisory board. Dr. Graff-Radford has received personal compensation in an editorial capacity for The Neurologist. Dr. Graff-Radford has received research support from Janssen, Pfizer Inc., Medivation, Forest Laboratories Inc., and Allon. Dr. Younkin has nothing to disclose. Dr. Dickson has received personal compensation for activities with Neotope, Inc. as a consultant. Dr. Taner has nothing to disclose.Wednesday, April 30 2014, 2:00 pm-3:45 pm %U