GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE228956 Query DataSets for GSE228956
Status Public on Oct 10, 2023
Title Functional interrogation of twenty Type 2 Diabetes-associated genes using isogenic hESC-derived β-like cells (SNP chip)
Organism Homo sapiens
Experiment type SNP genotyping by SNP array
Summary Genetic studies have identified numerous loci associated with type 2 diabetes (T2D), but the functional role of many loci has remained unexplored. In this study, we engineered isogenic knockout human embryonic stem cell (hESC) lines for 20 genes associated with T2D risk. We systematically examined β-cell differentiation, insulin production and secretion, and survival. We performed RNA-seq and ATAC-seq on hESC-β cells from each knockout line. Analyses of T2D GWAS signals overlapping with HNF4A-dependent ATAC peaks identified a specific SNP as a likely causal variant. In addition, we performed integrative association analyses and identified four genes (CP, RNASE1, PCSK1N and GSTA2) associated with insulin production, and two genes (TAGLN3 and DHRS2) associated with sensitivity to lipotoxicity. Finally, we leveraged deep ATAC-seq read coverage to assess allele-specific imbalance at variants heterozygous in the parental hESC line, to identify a single likely functional variant at each of 23 T2D GWAS signals.
Overall design We genotyped the parental MEL1 hESC lines and generated imputed genotypes of all SNPs (r2>0.3) included in the TOPmed panel for the ATAC-seq allelic imbalance analysis.
Contributor(s) Xue D, Narisu N, Taylor DL, Zhang M, Grenko C, Yan T, Sinha N, Erdos MR, Bonnycastle LL, Chen S, Collins FS
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Apr 04, 2023
Last update date Oct 11, 2023
Contact name Shuibing Chen
Phone 2127465431
Organization name Weill Cornell Medical College
Department Surgery
Street address A 827B, 1300 York Ave
City New York
State/province NY
ZIP/Postal code 10065
Country USA
Platforms (1)
GPL25201 InfiniumOmni2-5Exome-8v1-3_A1
Samples (1)
GSM7146178 MEL1
This SubSeries is part of SuperSeries:
GSE228665 Functional interrogation of twenty Type 2 Diabetes-associated genes using isogenic hESC-derived β-like cells
BioProject PRJNA952243

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
GSE228956_RAW.tar 452.3 Mb (http)(custom) TAR (of IDAT, TXT)
Processed data provided as supplementary file

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