Abstract
Clinical studies in type 2 diabetes (T2D) primarily focused on the single nucleotide polymorphisms (SNPs) located in protein-coding regions. Recently, the SNPs located in noncoding regions have also been recognized to play an important role in disease susceptibility. The super enhancer is a cluster of transcriptional enhancers located in noncoding regions. It plays a critical role in cell-type specific gene expression. However, the exact mechanism of the super enhancer SNPs for T2D remains unclear. In this study, we integrated genome-wide association studies (GWASs) and T2D cell/tissue-specific histone modification ChIP-seq data to identify T2D-associated SNPs in super enhancer, followed by comprehensive bioinformatics analyses to further explore the functional importance of these SNPs. We identified several interesting T2D super enhancer SNPs. Interesting, most of them were clustered within the same or neighboring super enhancers. A number of SNPs are involved in chromatin interactive regulation and/or potentially influence the binding affinity of transcription factors. Gene Ontology (GO) analysis showed a significant enrichment in several well-known signaling pathways and regulatory process, e.g. WNT signaling pathway, which plays a key role in T2D metabolism. Our results highlighted the potential functional importance of T2D super enhancer SNPs, which may yield novel insights into the pathogenesis of T2D.
Highlights
Type 2 diabetes (T2D) is a long-term metabolic disorder which is characterized by hyperglycemia and the aberrant metabolism of fat and protein due to the deficient action of insulin [1]
1,086 potential functional T2D single nucleotide polymorphisms (SNPs) were mapped to the identified T2D cell/tissue-specific super enhancer
Our results indicate a total of 286 potential functional T2D super enhancer SNPs
Summary
Type 2 diabetes (T2D) is a long-term metabolic disorder which is characterized by hyperglycemia and the aberrant metabolism of fat and protein due to the deficient action of insulin [1].
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