小说晚发性阿尔茨海默病大脑位点变异与基因表达(S54.001)

文摘

摘要目的:确定任何小说的负载GWAS风险位点变异影响大脑的基因表达水平。

背景最近的全基因组关联研究(GWAS)迟发性阿尔茨海默氏症(负载)确定九小说风险位点。内发现的功能变体基因在这些位点必须确认他们在广告的角色。我们假设一些小说的负载GWAS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:我们测量基因表达水平在小脑和颞叶皮层的大脑解剖广告主题,那些与其他疾病(773大脑样本)。确定任何风险变异eSNPs小说的负载,我们测试了他们的协会与表达六附近(cis)负载候选基因检测在人类大脑(ABCA7、BIN1 CLU, MS4A4A MS4A6A, PICALM)和额外的13个基因±100 kb的这些单核苷酸多态性。影响大脑识别额外eSNPs小说候选人负载基因表达水平的基因,我们确定了snp±100 kb的位置和检测cis-associations。

结果:负荷风险snp CLU, MS4A4A位点显著影响颞叶皮层这些基因的表达水平。LOAD-protective CLU和高风险MS4A4A位点等位基因与大脑的这些基因水平更高。此外,还有其他cis-variants显著影响大脑CLU, ABCA7的表情。

结论:CLU, MS4A4A eSNPs可能至少部分解释了负载在这些位点风险协会。CLU, ABCA7可能港口额外eSNPs强劲。这些结果具有广泛的意义在小说的搜索功能变体负荷风险位点。

支持:R01AG032990,P50AG016574,KL2 RR024151。

披露:艾伦博士没有披露。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。Maharjan博士没有披露。 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. 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. Dr. Taner has nothing to disclose.