26-OR: Meta-analyses of Genome-Wide Association Studies for Proinsulin Provide Insight into Glycemic Trait Dysregulation

Proinsulin, a prohormone precursor to insulin, is synthesized and processed before secretion from pancreatic islet beta cells. Increased plasma proinsulin levels relative to insulin levels may predict insulin resistance and type 2 diabetes (T2D), and the genes involved in proinsulin processing are incompletely understood. Previous genome-wide association studies (GWAS) have identified 13 loci associated with proinsulin levels. To identify additional loci, we conducted a meta-analysis of GWAS results of fasting proinsulin from 16 European-ancestry studies of 45,826 individuals. Each cohort analysis controlled for age, sex, population structure, fasting insulin, and BMI. We identified 35 independent association signals at 30 loci (1 Mb, p