Year: 2014
Type: review
Study design: Observational Study
Abstract: Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.
Source: PLoS Genetics
Authors: Inga Prokopenko, Wenny Poon, Reedik Mägi, Rashmi Prasad B, S. Albert Salehi, Peter Almgren, Peter Osmark, Nabila Bouatia-Naji, Nils Wierup, Tove Fall, Alena Stančáková, Adam Barker, Vasiliki Lagou, Clive Osmond, Weijia Xie, Jari Lahti, Anne U. Jackson, Yu-Ching Cheng, Jie Liu, Jeffrey R. O'Connell, Paul A. Blomstedt, Joao Fadista, Sami Alkayyali, Tasnim Dayeh, Emma Ahlqvist, Jalal Taneera, Cecile Lecoeur, Ashish Kumar, Ola Hansson, Karin Hansson, Benjamin F. Voight, Hyun Min Kang, Claire Levy-Marchal, Vincent Vatin, Aarno Palotie, Ann-Christine Syvänen, Andrea Mari, Michael N. Weedon, Ruth J. F. Loos, Ken K. Ong, Peter Nilsson, Bo Isomaa, Tiinamaija Tuomi, Nicholas J. Wareham, Michael Stumvoll, Elisabeth Widen, Timo A. Lakka, Claudia Langenberg, Anke Tönjes, Rainer Rauramaa, Johanna Kuusisto, Timothy M. Frayling, Philippe Froguel, Mark Walker, Johan G. Eriksson, Charlotte Ling, Peter Kovacs, Erik Ingelsson, Mark I. McCarthy, Alan R. Shuldiner, Kristi D. Silver, Markku Laakso, Leif Groop, Valeriya Lyssenko
Institutions: Centre for Human Genetics, Hammersmith Hospital, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Imperial College London, Lund University, University of Tartu, Centre National de la Recherche Scientifique, Inserm, Institut Pasteur de Lille, Paris Cardiovascular Research Center, (Epi)génomique fonctionnelle métabolique et des dysfonctions dans le diabète de type 2 et des maladies associées, Université Lille Nord de France, Uppsala University, Science for Life Laboratory, University of Eastern Finland, Kuopio University Hospital, University of Cambridge, MRC Epidemiology Unit, MRC Lifecourse Epidemiology Unit, University of Southampton, University of Exeter, Peninsula College of Medicine and Dentistry, University of Helsinki, Folkhälsans Forskningscentrum, University of Michigan, University of Maryland, Baltimore, Åbo Akademi University, Finnish Institute for Health and Welfare, Swiss Tropical and Public Health Institute, University of Basel, University of Pennsylvania, Hôpital Robert-Debré, Broad Institute, Harvard University, Helsinki University Hospital, Wellcome Sanger Institute, Institute for Molecular Medicine Finland, Massachusetts Institute of Technology, National Research Council, Skåne University Hospital, IFB Adiposity Diseases, Leipzig University, Newcastle University, Churchill Hospital, NIHR Oxford Biomedical Research Centre, Steno Diabetes Centers
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: U.S. Department of Agriculture, Eli Lilly and Company, AstraZeneca, Sanofi, Johns Hopkins University, Wellcome Trust, National Institute for Health and Care Research, Diabetes UK, European Commission, European Science Foundation, European Foundation for the Study of Diabetes, Deutsche Forschungsgemeinschaft, Royal Swedish Academy of Sciences, Stiftelsen för Strategisk Forskning, Kela, Academy of Finland, Bundesministerium für Bildung und Forschung, Lunds Universitet, Hjärt-Lungfonden, Juho Vainion Säätiö, Kuopion Yliopistollinen Sairaala, Novo Nordisk, Signe ja Ane Gyllenbergin Säätiö, Vetenskapsrådet, Emil Aaltosen Säätiö, Svenska Kulturfonden, Svenska Läkaresällskapet, Tartu Ülikool, Diabetesliitto, Boehringer Ingelheim Stiftung, Science for Life Laboratory, Novo Nordisk Fonden, National Institutes of Health, National Institute of Food and Agriculture, Medical Research Council, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, NIH Clinical Center, Mid-Atlantic Nutrition Obesity Research Center, School of Medicine, University of Maryland
Awards: G119964413, G1438682972, G1455670351, G1524424421, G1658607246, G1695511752, General and targeted approaches to unraveling the molecular causes of type 2 diabetes, ANDIS - All New Diabetics in Scania. A first step towards individualized medicine in diabetes care., Next-Generation Disease Association Analyses: Low pass Sequencing and High Density SNP genotyping for type 2 diabetes ., G2004031785, G2050560213, G2109279595, G2375955327, Diabetes Research and Training Center, G2473961061, Characterising causal alleles for common disease., G263730981, General Clinical Research Center, G292827090, G2973790809, G2997716172, G3067760959, G3207356259, G3227761751, An investigation of genes in key beta-cell pathways following the type 2 diabetes WTCCC genome wide association study., G3429936037, Genome-wide Association in Families: Data Integrity, Design and Methods Issue, General Clinical Research Center, G3588481721, G3728971702, G3865460896, G386878553, G393177772, G4280428318, Integriertes Forschungs- und Behandlungszentrum AdipositasErkrankungen, European Network for Genetic and Genomic Epidemiology, G4760961572, G4855546878, Genetics of Diabetes in the Amish, G5034709075, G5082768459, G5455155326, G5517677352, G5571867242, G5594960057, G5702163051, NIHR Senior Investigator Award, G6079663390, G6367303130, G67379338, G6957823285, Mid-Atlantic Nutrition Obesity Research Center, Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics., G7242858263, G729486055, G7318710736, G78824551, G8170210843, G82803878, G8323869059, Linkage of 15q to Insulin Levels in the Old Order Amish, NIHR Senior Investigator Award, G8655762198, G8713346975, G9000001730, G9000034868
OpenAlex ID: W2158005146