PLoS ONE (Jan 2011)

The genetic effect of copy number variations on the risk of type 2 diabetes in a Korean population.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0019091
Journal volume & issue
Vol. 6, no. 4
p. e19091

Abstract

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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.