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

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 0.8) with the GWAS index SNP rs7172432.

Source: The American Journal of Human Genetics - April 5, 2018 Category: Genetics & Stem Cells Authors: Ina Kycia, Brooke N. Wolford, Jeroen R. Huyghe, Christian Fuchsberger, Swarooparani Vadlamudi, Romy Kursawe, Ryan P. Welch, Ricardo d ’Oliveira Albanus, Asli Uyar, Shubham Khetan, Nathan Lawlor, Mohan Bolisetty, Anubhuti Mathur, Johanna Kuusisto, Markku Tags: Article Source Type: research