A Common Type 2 Diabetes Risk Variant Potentiates Activity of an Evolutionarily Conserved Islet Stretch Enhancer and Increases C2CD4A and C2CD4B Expression.

ABSTRACT: Genome-wide association studies (GWASs) and functional genomics approaches implicate enhancer disruption in islet dysfunction and type 2 diabetes (T2D) risk. We applied genetic fine-mapping and functional (epi)genomic approaches to a T2D- and proinsulin-associated 15q22.2 locus to identify a most likely causal variant, determine its direction of effect, and elucidate plausible target genes. Fine-mapping and conditional analyses of proinsulin levels of 8,635 non-diabetic individuals from the METSIM study support a single association signal represented by a cluster of 16 strongly associated (p < 10^-17) variants in high linkage disequilibrium (r² > 0.8) with the GWAS index SNP rs7172432. These variants reside in an evolutionarily and functionally conserved islet and β ce

SUBMITTER: Kycia I 

PROVIDER: S-EPMC5985342 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature