Journal Article

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

Emilsson, Valur, Morris, Andrew P, Luan, Jian'an, Stringham, Heather M, Chines, Peter S, Forsen, Tom, Khan, Hassan, Hunt, Sarah E, James, Alan, Fraser, Ross M, Guiducci, Candace, Männistö, Satu, Fox, Caroline, Tikkanen, Emmi, Esko, Tonu, Edkins, Sarah, Kao, Wen Hong L, Kraft, Peter, Lobbens, Stéphane, Chen, Han, Grant, George B, Robertson, Neil, Liu, Ching-Ti, Lawrence, Robert, Groves, Christopher J, Strawbridge, Rona J, Kravic, Jasmina, van Dam, Rob M, Meyer, Julia, Leander, Karin, Lindholm, Eero, Loos, Ruth J F, Langenberg, Claudia, Eury, Elodie, Voight, Benjamin F, Ferreira, Teresa, Yengo, Loic, Vedantam, Sailaja, Rossin, Elizabeth J, Rehnberg, Emil, Kumar, Ashish, Sivapalaratnam, Suthesh, Kong, Augustine, Wiltshire, Steven, Müller-Nurasyid, Martina, Wood, Andrew R, Gigante, Bruna, Florez, Jose C, Crenshaw, Andrew T, Klopp, Norman, Hui, Jennie, Lagou, Vasiliki, Herder, Christian, Potter, Simon, Bonnycastle, Lori L, Thorleifsson, Gudmar, Lindgren, Cecilia M, Platou, Carl G P, Charpentier, Guillaume, Krjutškov, Kaarel, Burtt, Noël, Segrè, Ayellet V, Couper, David J, Holmen, Oddgeir L, Almgren, Peter, Gertow, Kar

2012

Overview

Mark McCarthy, Michael Boehnke, Andrew Morris and colleagues perform large-scale association analyses using the Metabochip to gain insights into the genetic architecture of type 2 diabetes. They report several new susceptibility loci, including two that show sex-differentiated effects on disease risk. To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/2489/144 / 692/699/2743/137/773 / Agriculture / Animal Genetics and Genomics / Annan klinisk medicin / Architecture / Biological and medical sciences / Biomedicine / Cancer Research / Cardiology and Cardiovascular Disease / Case-Control Studies / Clinical Medicine / Development and progression / Diabetes / Diabetes Mellitus, Type 2 - epidemiology / Diabetes Mellitus, Type 2 - genetics / Diabetes. Impaired glucose tolerance / Endocrine pancreas. Apud cells (diseases) / Endocrinology and Diabetes / Endocrinopathies / Endokrinologi och diabetes / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Fundamental and applied biological sciences. Psychology / Gene Function / Genealogy / Genes - physiology / Genetic aspects / Genetic Predisposition to Disease - genetics / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study - statistics & numerical data / Genomes / Heart attacks / Human Genetics / Humans / Kardiologi och kardiovaskulära sjukdomar / Klinisk medicin / Linkage Disequilibrium / Male / Medical and Health Sciences / Medical sciences / Medicin och hälsovetenskap / Meta-analysis / Metabolic disorders / Myocardial infarction / Other Clinical Medicine / Pakistan - epidemiology / Physiological aspects / Polymorphism, Single Nucleotide - physiology / Sex Factors / Type 2 diabetes