染色质
生物
人脑
电池类型
计算生物学
嘉雅宠物
神经科学
遗传学
疾病
基因
染色质重塑
细胞
医学
病理
作者
Biao Zeng,Jaroslav Bendl,Chengyu Deng,Donghoon Lee,R. Misir,Sarah M. Reach,Steven P. Kleopoulos,Pavan K. Auluck,Stefano Marenco,David A. Lewis,Vahram Haroutunian,Nadav Ahituv,John F. Fullard,Gabriel E. Hoffman,Panos Roussos
标识
DOI:10.1101/2023.03.02.530826
摘要
Nucleotide variants in cell type-specific gene regulatory elements in the human brain are major risk factors of human disease. We measured chromatin accessibility in sorted neurons and glia from 1,932 samples of human postmortem brain and identified 34,539 open chromatin regions with chromatin accessibility quantitative trait loci (caQTL). Only 10.4% of caQTL are shared between neurons and glia, supporting the cell type specificity of genetic regulation of the brain regulome. Incorporating allele specific chromatin accessibility improves statistical fine-mapping and refines molecular mechanisms underlying disease risk. Using massively parallel reporter assays in induced excitatory neurons, we screened 19,893 brain QTLs, identifying the functional impact of 476 regulatory variants. Combined, this comprehensive resource captures variation in the human brain regulome and provides novel insights into brain disease etiology.
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