论文题目: | Functional Genomics Reveal Gene Regulatory Mechanisms Underlying Schizophrenia Risk |
作者: | Huo Y, Li S, Liu J, Li X, Luo XJ |
联系作者: | luoxiongjian@mail.kiz.ac.cn |
发表年度: | 2019 |
DOI: | doi: 10.1038/s41467-019-08666-4 |
摘要: |
Genome-wide association studies (GWASs) have identified over 180 independent schizophrenia risk loci. Nevertheless, how the risk variants in the reported loci confer schizophrenia susceptibility remains largely unknown. Here we systematically investigate the gene regulatorymechanisms underpinning schizophrenia risk through integrating data from functional genomics (including 30 ChIP-Seq experiments) and position weight matrix (PWM). We identify 132 risk single nucleotide polymorphisms (SNPs) that disrupt transcription factor binding and we find that 97 of the 132 TF binding-disrupting SNPs are associated with gene expression in human brain tissues. We validate the regulatoryeffect of some TF binding-disrupting SNPs with reporter gene assays (9 SNPs) and allele-specific expression analysis (10 SNPs). Our study reveals gene regulatory mechanisms affected by schizophrenia risk SNPs (including widespread disruption of POLR2A and CTCF binding) and identifies target genes for mechanistic studies and drug development. Our results can be accessed and visualized at SZDB database ( http://www.szdb.org/ ) |
刊物名称: | Nature Communications |
论文出处: | https://www.nature.com/articles/s41467-019-08666-4 |
影响因子: | 12.353(2017年) |