Highlights
- •CNV analysis was carried out on a total of 1715 individuals from 12 populations.
- •34.4% of the total population to be under CNV burden for T2DM.
- •Eighty-three disease causal and associated genes were found under CNV influence.
- •Overlap studies with case cohorts revealed CNV influence on significant disease risk genes such as EGFR, E2F1, PPP1R3A, HLA and TSPAN8.
Abstract
Aims
To identify the role of copy number variations (CNVs) on disease risk genes and its
effect on disease phenotypes in type 2 diabetes mellitus (T2DM) in 12 random populations
using high throughput arrays.
Methods
CNV analysis was carried out on a total of 1715 individuals from 12 populations, from
ArrayExpress Archive of the European Bioinformatics Institute along with our subjects
using Affymetrix Genome Wide SNP 6.0 array. CNV effect on T2DM genes were analyzed
using several bioinformatics tools and a molecular protein interaction network was
constructed to identify the disease mechanism altered by the CNVs.
Results
Analysis showed 34.4% of the total population to be under CNV burden for T2DM, with
83 disease causal and associated genes being under CNV influence. Hotspots were identified
on chromosomes 22, 12, 6, 19 and 11.Overlap studies with case cohorts revealed significant
disease risk genes such as EGFR, E2F1, PPP1R3A, HLA and TSPAN8.
Conclusions
CNVs play a significant role in predisposing T2DM in normal cohorts and contribute
to the phenotypic effects. Thus, CNVs should be considered as one of the major contributors
in predisposition of the disease.
Keywords
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Article info
Publication history
Published online: January 13, 2016
Accepted:
December 26,
2015
Received in revised form:
December 3,
2015
Received:
August 5,
2015
Identification
Copyright
© 2016 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
