Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

  title={Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes},
  author={Rona J. Strawbridge and Jos{\'e}e Dupuis and Inga Prokopenko and Adam Barker and Emma Ahlqvist and Denis V. Rybin and John R Petrie and Mary E. Travers and Nabila Bouatia-Naji and Antigone S. Dimas and Alexandra C. Nica and Eleanor Wheeler and Han Chen and Benjamin F. Voight and Jalal Taneera and Stavroula Kanoni and John F. Peden and Fabiola Turrini and Stefan Gustafsson and Carina A Zabena and Peter Almgren and David J. P. Barker and Daniel R Barnes and Elaine M. Dennison and Johan G Eriksson and Per Eriksson and Elodie Eury and Lasse Folkersen and Caroline Fox and Timothy M. Frayling and Anuj Goel and Harvest F Gu and Momoko Horikoshi and Bo Isomaa and Anne U. Jackson and Karen A. Jameson and Eero O. Kajantie and Julie Kerr-conte and Teemu Kuulasmaa and Johanna Kuusisto and Ruth J. F. Loos and Jian'an Luan and Konstantinos Makrilakis and Alisa Knodle Manning and Mar{\'i}a Teresa Mart{\'i}nez-Larrad and Narisu Narisu and Maria Nastase Mannila and John {\"O}hrvik and Clive Osmond and Laura Pascoe and Felicity Payne and Avan Aihie Sayer and Bengt Sennblad and Angela Silveira and Alena Stan{\vc}{\'a}kov{\'a} and Kathy Stirrups and Amy J. Swift and Ann-Christine Syv{\"a}nen and Tiinamaija Tuomi and Ferdinand M. van 't Hooft and Mark Walker and M. N. Weedon and Weijia Xie and Bj{\"o}rn Zethelius and Halit Ongen and Anders M{\"a}larstig and Jemma C. Hopewell and Danish Saleheen and John Campbell Chambers and Sarah Parish and John Danesh and Jaspal Singh Kooner and Claes-G{\"o}ran {\"O}stenson and Lars Lind and Cyrus C. Cooper and Manuel Serrano-R{\'i}os and Ele Ferrannini and Tom J. Forsen and Robert J. Clarke and Maria Grazia Franzosi and Udo Seedorf and Hugh C Watkins and Philippe Froguel and Paul P.V. Johnson and Panagiotis Deloukas and Francis S. Collins and Markku Laakso and Emmanouil T. Dermitzakis and Michael Boehnke and Mark I. McCarthy and Nicholas J Wareham and Leif Groop and François Pattou and Anna L Gloyn and George V. Z. Dedoussis and Valeriya Lyssenko and James B. Meigs and In{\^e}s Barroso and Richard M. Watanabe and Erik Ingelsson and Claudia Langenberg and Anders Hamsten and Jose C Florez},
OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-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… CONTINUE READING
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