The Genetic Effect of Copy Number Variations on the Risk of Type 2 Diabetes in a Korean Population

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Apr 29

PMID 21526130

Citations 13

Authors

Joon Seol Bae

Hyun Sub Cheong

Ji-Hong Kim

Byung Lae Park

Jeong-Hyun Kim

Tae Joon Park

Jason Yongha Kim

Charisse Flerida A Pasaje

Jin Sol Lee

Yun-Ju Park

Miey Park

Chan Park

Insong Koh

Yeun-Jun Chung

Jong-Young Lee

Hyoung Doo Shin

Affiliations

Soon will be listed here.

Abstract

Background: Unlike Caucasian populations, genetic factors contributing to the risk of type 2 diabetes mellitus (T2DM) are not well studied in Asian populations. In light of this, and the fact that copy number variation (CNV) is emerging as a new way to understand human genomic variation, the objective of this study was to identify type 2 diabetes-associated CNV in a Korean cohort.

Methodology/principal Findings: Using the Illumina HumanHap300 BeadChip (317,503 markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 275 patients with type 2 diabetes mellitus (T2DM) and 496 nondiabetic subjects (Total n = 771). To increase the sensitivity of CNV identification, we incorporated multiple factors using PennCNV, a program that is based on the hidden Markov model (HMM). To assess the genetic effect of CNV on T2DM, a multivariate logistic regression model controlling for age and gender was used. We identified a total of 7,478 CNVs (average of 9.7 CNVs per individual) and 2,554 CNV regions (CNVRs; 164 common CNVRs for frequency>1%) in this study. Although we failed to demonstrate robust associations between CNVs and the risk of T2DM, our results revealed a putative association between several CNVRs including chr15:45994758-45999227 (P = 8.6E-04, P(corr) = 0.01) and the risk of T2DM. The identified CNVs in this study were validated using overlapping analysis with the Database of Genomic Variants (DGV; 71.7% overlap), and quantitative PCR (qPCR). The identified variations, which encompassed functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the development process, in cell communication, in signal transduction, and in biological regulation.

Conclusion/significance: We expect that the methods and findings in this study will contribute in particular to genome studies of Asian populations.

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