小说进行性核上的麻痹大脑(PSP)风险位点变异与基因表达水平(S54.002)

文摘

摘要目的:确定任何小说的PSP GWAS风险位点变异影响大脑的基因表达水平。

背景在最近的PSP,四个位点附近MAPT,STX6,EIF2AK3,MOBP赋予重大风险,除了三个暗示位点1 q41基因间的轨迹,BMS1和SLCO1A2。修改脑基因表达的基因变异也可能影响人类疾病的风险。我们假设一些小说的PSP位点变异赋予疾病风险通过影响大脑的基因表达水平。

设计/方法:我们测量773年24526转录表达水平大脑小脑样本和颞叶皮层的解剖对象与阿尔茨海默氏症(广告,小脑n = 197,颞叶皮层n = 202)和其他大脑疾病(non-AD,小脑n = 177,颞叶皮层n = 197),包括患者PSP(小脑n = 98,颞叶皮层n = 107)。我们一个表达式进行全基因组关联研究(eGWAS)使用213528年独联体单核苷酸多态性在±100 kb的测试记录。我们评估了七个最强的PSP风险位点在我们eGWAS协会的表达水平附近的成绩单。

结果:我们发现的证据独联体PSP风险之间的关联变异和大脑的表达水平SLCO1A2,MAPT和MOBP。许多小脑之间的关联复制和颞叶皮层组织,以及在不同的病理诊断。

结论:SLCO1A2,MAPT和MOBPeSNPs可能至少部分解释了PSP风险协会在这些位点。这些结果具有广泛的意义在小说的搜索功能变体PSP风险位点。此外,他们认为,疾病相关独联体SNP可能会影响基因表达独立的大脑区域或病理学和可靠地映射在组织的影响和影响的学科。

支持:R01AG032990,P50AG016574,KL2 RR024151。

披露:谭博士没有披露。邹博士没有披露。茶博士没有披露。Younkin博士没有披露。克鲁克博士没有披露。Pankratz说道已收到博士研究雅培公司的支持,公司艾伦博士没有披露。Carrasquillo博士没有披露。博士罗利没有披露。奈尔博士没有披露。Middha博士没有披露。 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. Palusak has nothing to disclose. Dr. Lincoln has nothing to disclose. Dr. Bisceglio has nothing to disclose. Dr. Georgescu has nothing to disclose. Dr. Kouri 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., Janssen Alzheimer's Immunotherapy, Elan Pharmaceuticals, and GE Healthcare. Dr. Graff-Radford has received personal compensation for activities with Codman as a participant on 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 Pharmaceuticals, Inc., Pfizer Inc, Medivation, Inc., Forrest Laboratories and Allon Therapeutics Inc. Dr. Dickson has nothing to disclose. Dr. Younkin has nothing to disclose.