Damaging missense variants in IGF1R implicate a role for IGF-1 resistance in the etiology of type 2 diabetes
Eugene J. Gardner, Katherine A. Kentistou, Stasa Stankovic, Sam Lockhart, Eleanor Wheeler, Felix R. Day, Nicola D. Kerrison, Nicholas J. Wareham, Claudia Langenberg, Stephen O’Rahilly, Ken K. Ong, John R. B. Perry
Abstract
), indicating relative IGF-1 resistance. A likely causal role of IGF-1 resistance was supported by Mendelian randomization analyses using common variants. These results increase understanding of the genetic architecture of T2D and highlight the growth hormone/IGF-1 axis as a potential therapeutic target.
Topics & Concepts
Missense mutationMendelian randomizationType 2 diabetesExomeGeneticsOdds ratioBiologyPopulationExome sequencingAllelePTENInternal medicineEndocrinologyMedicineGeneMutationDiabetes mellitusGenotypePI3K/AKT/mTOR pathwayGenetic variantsEnvironmental healthApoptosisGrowth Hormone and Insulin-like Growth FactorsGenetic Associations and EpidemiologyMetabolism, Diabetes, and Cancer