Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study.

ABSTRACT: Glucagon-like peptide 1 (GLP-1) stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS) of GLP-1 stimulated insulin secretion in non-diabetic individuals from the Netherlands Twin register (n = 126). This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100). Additionally, a polygenic risk score based on SNPs prioritized from the network was associa

SUBMITTER: Gudmundsdottir V 

PROVIDER: S-EPMC5749727 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature