大脑的表情全基因组关联研究(eGWAS)识别人类疾病有关的变异(P05.069)

文摘

摘要目的:确定监管变异的贡献影响大脑基因表达水平(eSNPs)人类中枢神经系统(CNS)和non-CNS疾病。

背景修改脑基因表达的基因变异也可能影响人类疾病的风险。我们假设大脑eSNPs丰富的遗传变异与人类疾病。

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)。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。

结果:我们确认2980小脑独联体SNP /协会重要的广告和non-ADs转录水平。其中,2087人在颞叶皮层也重要。顶部小脑独联体snp 2.4倍浓缩了人类疾病相关变异(p < 10⁶)。我们确定了小说独联体SNP /记录协会对人类疾病有关的变异,包括中枢神经系统疾病,如进行性核上的麻痹和帕金森病。我们也确认了独联体单核苷酸多态性与中枢神经系统疾病和其他non-CNS疾病,如系统性红斑狼疮和1型糖尿病。

结论:大脑的重要的浓缩独联体单核苷酸多态性与疾病有关的变异主张基因表达变化机制,许多中枢神经系统和non-CNS疾病。结合评估表达式和疾病GWAS可能提供补充信息发现的人类疾病变异与功能的影响。我们的研究结果有影响的设计和解释eGWAS一般和大脑的使用表达在人类疾病的研究数量性状遗传。

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.