作者
Alexi Nott, Inge R Holtman, Nicole G Coufal, Johannes CM Schlachetzki, Miao Yu, Rong Hu, Claudia Z Han, Monique Pena, Jiayang Xiao, Yin Wu, Zahara Keulen, Martina P Pasillas, Carolyn O’Connor, Christian K Nickl, Simon T Schafer, Zeyang Shen, Robert A Rissman, James B Brewer, David Gosselin, David D Gonda, Michael L Levy, Michael G Rosenfeld, Graham McVicker, Fred H Gage, Bing Ren, Christopher K Glass
发表日期
2019/11/29
期刊
Science
卷号
366
期号
6469
页码范围
1134-1139
出版商
American Association for the Advancement of Science
简介
Noncoding genetic variation is a major driver of phenotypic diversity, but functional interpretation is challenging. To better understand common genetic variation associated with brain diseases, we defined noncoding regulatory regions for major cell types of the human brain. Whereas psychiatric disorders were primarily associated with variants in transcriptional enhancers and promoters in neurons, sporadic Alzheimer’s disease (AD) variants were largely confined to microglia enhancers. Interactome maps connecting disease-risk variants in cell-type–specific enhancers to promoters revealed an extended microglia gene network in AD. Deletion of a microglia-specific enhancer harboring AD-risk variants ablated BIN1 expression in microglia, but not in neurons or astrocytes. These findings revise and expand the list of genes likely to be influenced by noncoding variants in AD and suggest the probable cell types in …
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