Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

R.J. Strawbridge, J. Dupuis, I. Prokopenko, A. Barker, E. Ahlqvist, D. Rybin, J.R. Petrie, N. Bouatia-Naji, A.S. Dimas, A. Nica, E. Wheeler, H. Chen, B.F. Voight, J. Taneera, S. Kanoni, J.J. Hottenga, E.J.C. de Geus, G. Willemsen, D.I. Boomsma, T.J. ForsenR. Clarke, M.G. Franzosi, U. Seedorf, H. Watkins, P. Froguel, P. Johnson, P. Deloukas, F.S. Collins, M. Laakso, E.T. Dermitzakis, M. Boehnke, M.I. McCarthy, N.J. Wareham, L. Groop, F. Pattou, A.L. Gloyn, G.V. Dedoussis, V. Lyssenko, J.B. Meigs, I. Barroso, R.M. Watanabe, E. Ingelsson, C. Langenberg, A. Hamsten, J.C. Florez

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10
Original languageEnglish
Pages (from-to)2624-2634
JournalDiabetes
Volume60
Issue number10
DOIs
Publication statusPublished - 2011

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