Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
Broadaway KA., Yin X., Williamson A., Parsons VA., Wilson EP., Moxley AH., Vadlamudi S., Varshney A., Jackson AU., Ahuja V., Bornstein SR., Corbin LJ., Delgado GE., Dwivedi OP., Fernandes Silva L., Frayling TM., Grallert H., Gustafsson S., Hakaste L., Hammar U., Herder C., Herrmann S., Højlund K., Hughes DA., Kleber ME., Lindgren CM., Liu C-T., Luan J., Malmberg A., Moissl AP., Morris AP., Perakakis N., Peters A., Petrie JR., Roden M., Schwarz PEH., Sharma S., Silveira A., Strawbridge RJ., Tuomi T., Wood AR., Wu P., Zethelius B., Baldassarre D., Eriksson JG., Fall T., Florez JC., Fritsche A., Gigante B., Hamsten A., Kajantie E., Laakso M., Lahti J., Lawlor DA., Lind L., März W., Meigs JB., Sundström J., Timpson NJ., Wagner R., Walker M., Wareham NJ., Watkins H., Barroso I., O'Rahilly S., Grarup N., Parker SC., Boehnke M., Langenberg C., Wheeler E., Mohlke KL.
Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value