Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes
Year: 2018
Type: article
Abstract: The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants ( LYPLAL1 , NEUROG3 , CAMKK2 , ABO , and GIP genes), one by a low-frequency ( EHMT2 ), and one driven by a rare variant in chromosome Xq23, rs146662075, associated with a twofold increased risk for T2D in males. rs146662075 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene ( AGTR2 ), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.
Source: Nature Communications
Authors: Sílvia Bonàs-Guarch, Marta Guindo-Martínez, Irene Miguel-Escalada, Niels Grarup, David Sebastian, Elias Rodriguez-Fos, Friman Sánchez, Mercè Planas-Fèlix, Paula Cortes-Sánchez, Santi González, Pascal Timshel, Tune H. Pers, Claire C. Morgan, Ignasi Moran, Goutham Atla, Juan R. González, Montserrat Puiggros, Jonathan Martí, Ehm A. Andersson, Carlos Díaz, Rosa M. Badia, Miriam Udler, Aaron Leong, Varindepal Kaur, Jason Flannick, Torben Jørgensen, Allan Linneberg, Marit E. Jørgensen, Daniel R. Witte, Cramer Christensen, Ivan Brandslund, Emil V. Appel, Robert A. Scott, Jian’an Luan, Claudia Langenberg, Nicholas J. Wareham, Oluf Pedersen, Antonio Zorzano, Jose C Florez, Torben Hansen, Jorge Ferrer, Josep Maria Mercader, David Torrents
Institutions: Barcelona Supercomputing Center, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Imperial College London, University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Institute for Research in Biomedicine, Barcelona Institute of Science and Technology, Universitat de Barcelona, Statens Serum Institut, Broad Institute, Boston Children's Hospital, Universitat Pompeu Fabra, Center for Research in Environmental Epidemiology, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Consejo Superior de Investigaciones Científicas, Artificial Intelligence Research Institute, Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard University, Capital Region of Denmark, Aalborg University, Glostrup Hospital, Rigshospitalet, University of Southern Denmark, Aarhus University, Danish Diabetes Academy, Vejle Sygehus, Lillebaelt Hospital, University of Cambridge, MRC Epidemiology Unit, Institució Catalana de Recerca i Estudis Avançats
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Eli Lilly and Company, Wellcome Trust, Steno Diabetes Center Copenhagen, National Institute for Health and Care Research, European Commission, European Foundation for the Study of Diabetes, Partnership for Advanced Computing in Europe AISBL, Generalitat de Catalunya, Ministerio de Economía y Competitividad, Lundbeckfonden, Novo Nordisk, Barcelona Supercomputing Center, Copenhagen Graduate School for Nanoscience and Nanotechnology, Novo Nordisk Fonden, Novo Nordisk Foundation Center for Basic Metabolic Research, Medical Research Council, Agència de Gestió d'Ajuts Universitaris i de Recerca, NIHR Imperial Biomedical Research Centre
Awards: Aetiology of type 2 diabetes and related metabolic disorders, G1634295611, G1869387299, High Throughput Science - Investigating the genetic determinants of healthy ageing: the MRC EPIC-Norfolk study, G2191045670, Analysis of tridimensional changes caused by type 2 Diabetes-Associated varianTs, G3023850977, Development of a systems biomedicine approach for risk identification, prevention and treatment of type 2 diabetes, G3812975344, G4321129689, G434337789, G518106951, G5418912364, Targeting etiologic molecular mechanisms to treat human diabetes, G6690247229, G6766900198, G6800011207, Understanding regulatory variation in human diabetes., Global initiative on gene-environment interaction on diabetes/obesity risk, NIHR Senior Investigator Award, G8491121283, NIHR Senior Investigator Award, The genetics of weight, BMI, adiposity and obesity, G959094345
OpenAlex ID: W2783331323