title: The genetic effect of copy number variations on the risk of type 2 diabetes in a Korean population.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  We expect that the methods and findings in this study will contribute in particular to genome studies of Asian populations.
authors.affiliation: Laboratory of Genomic Diversity, Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Tae Joon
authors.initials: TJ
authors.lastname: Park
authors.forename: Jason Yongha
authors.initials: JY
authors.lastname: Kim
authors.forename: Charisse Flerida A
authors.initials: CF
authors.lastname: Pasaje
authors.forename: Jin Sol
authors.initials: JS
authors.lastname: Lee
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Park
authors.forename: Miey
authors.initials: M
authors.lastname: Park
authors.forename: Chan
authors.initials: C
authors.lastname: Park
authors.forename: InSong
authors.initials: I
authors.lastname: Koh
authors.forename: Yeun-Jun
authors.initials: YJ
authors.lastname: Chung
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D044466:Asian People / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D056910:Republic of Korea