PMID- 21526130
OWN - NLM
STAT- MEDLINE
DCOM- 20110816
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 4
DP  - 2011 Apr 22
TI  - The genetic effect of copy number variations on the risk of type 2 diabetes in a 
      Korean population.
PG  - e19091
LID - 10.1371/journal.pone.0019091 [doi]
LID - e19091
AB  - 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.
FAU - Bae, Joon Seol
AU  - Bae JS
AD  - Laboratory of Genomic Diversity, Department of Life Science, Sogang University, 
      Seoul, Republic of Korea.
FAU - Cheong, Hyun Sub
AU  - Cheong HS
FAU - Kim, Ji-Hong
AU  - Kim JH
FAU - Park, Byung Lae
AU  - Park BL
FAU - Kim, Jeong-Hyun
AU  - Kim JH
FAU - Park, Tae Joon
AU  - Park TJ
FAU - Kim, Jason Yongha
AU  - Kim JY
FAU - Pasaje, Charisse Flerida A
AU  - Pasaje CF
FAU - Lee, Jin Sol
AU  - Lee JS
FAU - Park, Yun-Ju
AU  - Park YJ
FAU - Park, Miey
AU  - Park M
FAU - Park, Chan
AU  - Park C
FAU - Koh, InSong
AU  - Koh I
FAU - Chung, Yeun-Jun
AU  - Chung YJ
FAU - Lee, Jong-Young
AU  - Lee JY
FAU - Shin, Hyoung Doo
AU  - Shin HD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110422
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Asian People/*genetics
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 15/genetics
MH  - DNA Copy Number Variations/*genetics
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Logistic Models
MH  - Polymerase Chain Reaction
MH  - Reproducibility of Results
MH  - Republic of Korea
PMC - PMC3081314
COIS- Competing Interests: Authors HS Cheong, BL Park, and HD Shin are employed by SNP 
      Genetics, Inc. http://www.snp-genetics.com. JS Bae, JH Kim, TJ Park, JY Kim, CFA 
      Pasaje, JS Lee, JH Kim, YJ Park, M Park, C Park, IS Koh and YJ Chung declare that 
      they have no competing interests. All authors adhere to the PLoS ONE policies on 
      sharing data and materials.
EDAT- 2011/04/29 06:00
MHDA- 2011/08/17 06:00
PMCR- 2011/04/22
CRDT- 2011/04/29 06:00
PHST- 2010/10/25 00:00 [received]
PHST- 2011/03/28 00:00 [accepted]
PHST- 2011/04/29 06:00 [entrez]
PHST- 2011/04/29 06:00 [pubmed]
PHST- 2011/08/17 06:00 [medline]
PHST- 2011/04/22 00:00 [pmc-release]
AID - PONE-D-10-03973 [pii]
AID - 10.1371/journal.pone.0019091 [doi]
PST - epublish
SO  - PLoS One. 2011 Apr 22;6(4):e19091. doi: 10.1371/journal.pone.0019091.