| Literature DB >> 29358691 |
Sílvia Bonàs-Guarch1, Marta Guindo-Martínez1, Irene Miguel-Escalada2,3,4, Niels Grarup5, David Sebastian3,6,7, Elias Rodriguez-Fos1, Friman Sánchez1,8, Mercè Planas-Fèlix1, Paula Cortes-Sánchez1, Santi González1, Pascal Timshel5,9, Tune H Pers5,9,10,11, Claire C Morgan4, Ignasi Moran4, Goutham Atla2,3,4, Juan R González12,13,14, Montserrat Puiggros1, Jonathan Martí8, Ehm A Andersson5, Carlos Díaz8, Rosa M Badia8,15, Miriam Udler16,17, Aaron Leong17,18, Varindepal Kaur17, Jason Flannick16,17,19, Torben Jørgensen20,21,22, Allan Linneberg20,23,24, Marit E Jørgensen25,26, Daniel R Witte27,28, Cramer Christensen29, Ivan Brandslund30,31, Emil V Appel5, Robert A Scott32, Jian'an Luan32, Claudia Langenberg32, Nicholas J Wareham32, Oluf Pedersen5, Antonio Zorzano3,6,7, Jose C Florez16,17,33, Torben Hansen5,34, Jorge Ferrer2,3,4, Josep Maria Mercader35,36,37, David Torrents38,39.
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, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 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.Entities:
Mesh：
Year: 2018 PMID： 29358691 PMCID： PMC5778074 DOI： 10.1038/s41467-017-02380-9
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919