@article {YangS21.003作者= {Hyun-Sik杨和查尔斯·白Lei Yu和Lori Chibnik朱莉·施奈德和大卫·班尼特和菲利普De Jager}, title ={染色体位点的识别影响认知弹性神经病理学(S21.003)},体积={86}={16}补充数量,elocation-id = {S21.003} ={2016},出版商= {Wolters Kluwer健康,公司代表美国神经病学学会},文摘={目的:旨在找到认知弹性神经病理学的遗传因素。首页背景:认知弹性归因于大脑储备能力,认知储备,微分组织病理反应。此外,病态不经常占会引起明显的韧性。然而,遗传决定因素的认知弹性是未知的。方法:我们研究的一个子集参加宗教团体学习和拉什记忆和衰老项目(n = 979)。我们定义术语{\ textquotedblright} {\ textquotedblleft}残余认知是认知之间的差异直接死亡和认知的人口结构和常见neuropathologic指数预测的{\ textquoteright}年代老年痴呆症,脑血管疾病,路易的身体疾病,和海马硬化。残余的认知,进行了全基因组关联研究和基因在100 kb的暗示位点(p \ < 10 ^ 5),甲基化状态与残余认知测试。最后,这些暗示位点是否cis-expressive数量性状基因座(cis-eQTL)检查。结果:共8暗示染色体位点,这些位点和基因在100 kb: WARS2, UNC5C, MTHFD1L, AKAP12, VWDE, TMEM106B, AGR2 AGR3, DLGAP2。AKAP12,其中,WARS2 UNC5C AGR2, DLGAP2排列甲基化状态与残余认知相关。 The minor allele for TMEM106B locus (top SNP rs11509153G) was a cis-eQTL associated with a decrease in TMEM106B expression. Interestingly, AKAP12 and DLGAP2 are synaptic proteins with implications in cognitive reserve, while UNC5C contributes to neuronal vulnerability to neurotoxins. The TMEM106B locus (rs11509153G) was in strong linkage disequilibrium with a previously identified protective variant (rs1990622G) for TDP-43, a pathology that has not been routinely accounted for. Conclusions: We identified several chromosomal loci where evidences from genetic and epigenetic factors converge to suggest association with apparent cognitive resilience (measured as residual cognition), and in proximity to these loci are genes involved in synaptic function, neuronal vulnerability, and TDP-43 pathology.Disclosure: Dr. Yang has nothing to disclose. Dr. White has nothing to disclose. Dr. Yu has nothing to disclose. Dr. Chibnik has nothing to disclose. Dr. Schneider has received personal compensation for activities with AVID Radiopharmaceuticals, Inc. and GE Healthcare. Dr. Bennett has received personal compensation for activities with Danone, Inc., Dr. Willmar Schwabe Pharmaceuticals, KG Pharmaceuticals and Eli Lilly, Inc. as a consultant. Dr. De Jager has received research support from Biogen Idec and Genzyme.Monday, April 18 2016, 1:00 pm-3:00 pm}, issn = {0028-3878}, URL = {//www.ez-admanager.com/content/86/16_Supplement/S21.003}, eprint = {//www.ez-admanager.com/content}, journal = {Neurology} }