Functional genomics reveal gene regulatory mechanisms underlying schizophrenia risk View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Yongxia Huo, Shiwu Li, Jiewei Liu, Xiaoyan Li, Xiong-Jian Luo

ABSTRACT

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 regulatory mechanisms 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 regulatory effect 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/ ). More... »

PAGES

670

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-08666-4

    DOI

    http://dx.doi.org/10.1038/s41467-019-08666-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112022997

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30737407


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