Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 29358691.
- Also identified by DOI 10.1038/s41467-017-02380-9 and PMC identifier 5778074.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Chromosomes, Human, X
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Polymorphism, Single Nucleotide