Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Bonàs-Guarch, Sílvia  ORCID logo  https://orcid.org/0000-0002-2085-7488
Guindo-Martínez, Marta  ORCID logo  https://orcid.org/0000-0002-8099-9170
Miguel-Escalada, Irene  ORCID logo  https://orcid.org/0000-0003-3461-6404
Sebastian, David 

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.

Description

Keywords

Alleles, Chromosomes, Human, X, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Insulin Resistance, Male, Models, Genetic, Polymorphism, Single Nucleotide, Risk Factors

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

9

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
MRC (MC_PC_13046)
MRC (MC_PC_13048)
European Commission (602068)
Wellcome Trust (091310/Z/10/Z)
Relationships
Is derived from: