TY - JOUR
T1 - The genetic effect of copy number variations on the risk of type 2 diabetes in a Korean population
AU - Bae, Joon Seol
AU - Cheong, Hyun Sub
AU - Kim, Ji Hong
AU - Park, Byung Lae
AU - Kim, Jeong Hyun
AU - Park, Tae Joon
AU - Kim, Jason Yongha
AU - Pasaje, Charisse Flerida A.
AU - Lee, Jin Sol
AU - Park, Yun Ju
AU - Park, Miey
AU - Park, Chan
AU - Koh, In Song
AU - Chung, Yeun Jun
AU - Lee, Jong Young
AU - Shin, Hyoung Doo
PY - 2011
Y1 - 2011
N2 - 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, Pcorr = 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.
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, Pcorr = 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.
UR - https://www.scopus.com/pages/publications/79955548007
U2 - 10.1371/journal.pone.0019091
DO - 10.1371/journal.pone.0019091
M3 - Article
C2 - 21526130
AN - SCOPUS:79955548007
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e19091
ER -
