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| 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
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| 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.
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| 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.
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| 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 |
| E-mail(s) |
shuibing.chen@gmail.com
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| Phone |
2127465431
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| Organization name |
Weill Cornell Medical College
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| Department |
Surgery
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| Street address |
A 827B, 1300 York Ave
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
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| Samples (1) |
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| This SubSeries is part of SuperSeries: |
| GSE228665 |
Functional interrogation of twenty Type 2 Diabetes-associated genes using isogenic hESC-derived β-like cells |
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| Relations |
| BioProject |
PRJNA952243 |
| 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 |
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