NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE184050 Query DataSets for GSE184050
Status Public on Sep 16, 2021
Title Novel diabetes gene discovery through comprehensive characterization and integrative analysis of longitudinal gene expression changes
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Type 2 diabetes is a complex, systemic disease affected by both genetic and environmental factors. Previous research has identified genetic variants associated with type 2 diabetes risk, however gene regulatory changes underlying progression to disease are still largely unknown. We investigated RNA expression changes that occur during diabetes progression using a two-stage approach. In our discovery stage, we compared changes in gene expression using two longitudinally collected blood samples from subjects who transitioned to type 2 diabetes between the time points against those who did not with a novel analytical network approach. Our network methodology identified 17 networks, one of which was significantly associated with transition status. This 822-gene network harbors many genes novel to the type 2 diabetes literature, but is also significantly enriched for genes previously associated with type 2 diabetes in GWAS. In the validation stage, we queried associations of genetically determined expression with diabetes-related traits in a large biobank with linked electronic health records. We observed a significant enrichment of genes in our identified network whose genetically determined expression is associated with type 2 diabetes and other metabolic traits and validated 31 gene-level associations that have never been reported by previous type 2 diabetes GWAS. Finally, we performed functional validation, demonstrating that the genes in this network are enriched in enhancers that operate in human pancreatic islet cells. We present an innovative and systematic approach that identified and validated key gene expression changes associated with type 2 diabetes transition status and demonstrated their translational relevance in a large clinical resource.
 
Overall design Longitudinal whole blood transcriptome profile of T2D progression
 
Contributor(s) Below JE, Chen H
Citation(s) 35157052
Submission date Sep 13, 2021
Last update date Jul 14, 2022
Contact name Hung-Hsin Chen
E-mail(s) hung-hsin.chen.1@vumc.org
Organization name Vanderbilt University Medical Center
Department Vanderbilt Genetics Institute
Street address 2525 West End Ave., Suite 700
City Nashville
State/province TN
ZIP/Postal code 37203
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (116)
GSM5576716 T2D case sample 1
GSM5576717 T2D case sample 2
GSM5576718 T2D case sample 3
Relations
BioProject PRJNA762935
SRA SRP336885

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
GSE184050_CCHC_T2D_DEseq2_normalized_count.txt.gz 15.6 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