NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE188491 Query DataSets for GSE188491
Status Public on Jan 23, 2022
Title Chromatin accessibility mapping at schizophrenia GWAS risk loci reveals compound genetic effects impairing neurodevelopment and synaptic function in human neurons
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Here, in NEUROG2-induced human neurons, we identified 31 credible risk SNPs in 26 schizophrenia (SZ) risk loci that displayed allele-specific open chromatin (ASoC) and were likely to be functional. For the VPS45 locus showing the strongest ASoC, CRISPR/Cas9 editing of ASoC SNP (rs2027349) altered the local expression of VPS45 and AC244033.2 (a lncRNA), and a distal gene, C1orf54. Notably, the global expression changes in neurons correlated with post-mortem brain expression signatures of neuropsychiatric disorders. Neurons carrying risk allele exhibited increased dendritic complexity, synaptic puncta density and hyperactivity, which were partially reversed by knocking-down each cis-regulated gene (VPS45, AC244033.2, or C1orf54), suggesting phenotypic contribution from all three genes.
 
Overall design In NEUROG2-induced human neurons, we identified 31 credible risk SNPs in 26 schizophrenia (SZ) risk loci that displayed allele-specific open chromatin (ASoC) and were likely to be functional. For the VPS45 locus showing the strongest ASoC, CRISPR/Cas9 editing of ASoC SNP (rs2027349) altered the local expression of VPS45 and AC244033.2 (a lncRNA), and a distal gene, C1orf54. Our study reveals a compound effect of multiple genes at a single SZ locus that impairs neurodevelopment and synaptic function, providing a mechanistic link between a noncoding SZ risk variant and disease-related cellular phenotypes.
 
Contributor(s) Jubao D, Siwei Z
Citation missing Has this study been published? Please login to update or notify GEO.
BioProject PRJNA778419
Submission date Nov 09, 2021
Last update date Jun 14, 2023
Contact name Jubao Duan
E-mail(s) jduan69@gmail.com
Phone (224) 364-7564
Organization name NorthShore University HealthSystem
Department Center for Psychiatric Genetics
Lab Unit of Functional Genomics in Psychiatry
Street address 1001 University Place
City Evanston
State/province IL
ZIP/Postal code 60201
Country USA
 
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (106)
GSM5683879 NGN2_ATAC_seq_line_02
GSM5683880 NGN2_ATAC_seq_line_03
GSM5683881 NGN2_ATAC_seq_line_04

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE188491_NGN2_Glut_20_lines_21Jun2021_peaks.narrowPeak.gz 5.2 Mb (ftp)(http) NARROWPEAK
GSE188491_RAW.tar 199.4 Gb (http)(custom) TAR (of BAM, TAR)
GSE188491_Raw_count_table_STAR_updated.txt.gz 1.8 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap