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Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Title: Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes
Authors: Bonàs Guarch, Sílvia; Guindo Martínez, Marta; Miguel-Escalada, Irene; Grarup, Niels; Sebastián Muñoz, David; Rodriguez-Fos, Elias; Sánchez, Friman; Planas-Fèlix, Mercè; Cortes-Sánchez, Paula; González, Santi; Timshel, Pascal; Pers, Tune H.; Morgan, Claire C.; Moran, Ignasi; Atla, Goutham; González, Juan Ramón; Puiggròs, Montserrat; Martí, Jonathan; Andersson, Ehm A.; Díaz, Carlos; Badia, Rosa M.; Udler, Miriam; Leong, Aaron; Kaur, Varindepal; Flannick, Jason; Jørgensen, Torben; Linneberg, Allan; Jørgensen, Marit E.; Witte, Daniel R.; Christensen, Cramer; Brandslund, Ivan; Appel, Emil V.; Scott, Robert A.; Luan, Jian'an; Langenberg, Claudia; Wareham, Nicholas J.; Pedersen, Oluf; Zorzano Olarte, Antonio; Florez, Jose C.; Hansen, Torben
Source: Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Publisher Information: Nature Publishing Group
Publication Year: 2018
Collection: Dipòsit Digital de la Universitat de Barcelona
Subject Terms: Diabetis; Genètica humana; Diabetes; Human genetics
Description: 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: Reproducció del document publicat a: https://doi.org/10.1038/s41467-017-02380-9; Nature Communications, 2018, vol. 9, num. 321; https://doi.org/10.1038/s41467-017-02380-9; info:eu-repo/grantAgreement/EC/H2020/658145/EU//3D-ADAPT; https://hdl.handle.net/2445/120954; 677009
Availability: https://hdl.handle.net/2445/120954
Rights: cc-by (c) Bonàs Guarch, Sílvia et al., 2018 ; http://creativecommons.org/licenses/by/3.0/es ; info:eu-repo/semantics/openAccess
Accession Number: edsbas.F1588C74
Database: BASE