Type 2 Diabetes Risk Alleles Are Associated With Reduced Size at Birth

Type 2 Diabetes Risk Alleles Are Associated With Reduced Size at Birth Rachel M. Freathy 1 , 2 , Amanda J. Bennett 3 , Susan M. Ring 4 , Beverley Shields 2 , Christopher J. Groves 3 , Nicholas J. Timpson 5 , 6 , Michael N. Weedon 1 , 2 , Eleftheria Zeggini 5 , Cecilia M. Lindgren 5 , Hana Lango 1 , 2 , John R.B. Perry 1 , 2 , Anneli Pouta 7 , 8 , Aimo Ruokonen 9 , Elina Hyppönen 10 , Chris Power 10 , Paul Elliott 11 , David P. Strachan 12 , Marjo-Riitta Järvelin 7 , 11 13 , George Davey Smith 4 , 6 , Mark I. McCarthy 3 , 5 , Timothy M. Frayling 1 , 2 and Andrew T. Hattersley 1 , 2 1 Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U.K.; 2 Department of Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U.K.; 3 Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.; 4 Department of Social Medicine, University of Bristol, Bristol, U.K.; 5 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.; 6 Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, U.K.; 7 National Public Health Institute, Oulu, Finland; 8 Department of Obstetrics and Gynecology, University of Oulu, Oulu, Finland; 9 Department of Clinical Chemistry, University of Oulu, Oulu, Finland; 10 MRC Centre of Epidemiology for Child Health, University College London Institute of Child Health, London, U.K.; 11 Department of Epidemiology and Public Health, Imperial College London, London, U.K.; 12 Division of Community Health Sciences, St. George's, University of London, London, U.K.; 13 Institute of Health, University of Oulu, Oulu, Finland. Corresponding author: Andrew T. Hattersley, andrew.hattersley{at}pms.ac.uk . Abstract OBJECTIVE Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight. RESEARCH DESIGN AND METHODS We genotyped single-nucleotide polymorphisms (SNPs) at five recently identified type 2 diabetes