TY - JOUR
T1 - Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes
AU - Bonàs-Guarch, Sílvia
AU - Guindo-Martínez, Marta
AU - Miguel-Escalada, Irene
AU - Grarup, Niels
AU - Sebastian, David
AU - Rodriguez-Fos, Elias
AU - Sánchez, Friman
AU - Planas-Fèlix, Mercè
AU - Cortes-Sánchez, Paula
AU - González, Santi
AU - Timshel, Pascal
AU - Pers, Tune H
AU - Morgan, Claire C
AU - Moran, Ignasi
AU - Atla, Goutham
AU - González, Juan R
AU - Puiggros, Montserrat
AU - Martí, Jonathan
AU - Andersson, Ehm A
AU - Díaz, Carlos
AU - Badia, Rosa M
AU - Udler, Miriam
AU - Leong, Aaron
AU - Kaur, Varindepal
AU - Flannick, Jason
AU - Jørgensen, Torben
AU - Linneberg, Allan
AU - Jørgensen, Marit E
AU - Witte, Daniel R
AU - Christensen, Cramer
AU - Brandslund, Ivan
AU - Appel, Emil V
AU - Scott, Robert A
AU - Luan, Jian'an
AU - Langenberg, Claudia
AU - Wareham, Nicholas J
AU - Pedersen, Oluf
AU - Zorzano, Antonio
AU - Florez, Jose C
AU - Hansen, Torben
AU - Ferrer, Jorge
AU - Mercader, Josep Maria
AU - Torrents, David
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-017-02380-9
DO - 10.1038/s41467-017-02380-9
M3 - Journal article
C2 - 29358691
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 321
ER -