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Myung Guen Chung 1 Article
Genetics
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Exome Chip Analysis of 14,026 Koreans Reveals Known and Newly Discovered Genetic Loci Associated with Type 2 Diabetes Mellitus
Seong Beom Cho, Jin Hwa Jang, Myung Guen Chung, Sang Cheol Kim
Diabetes Metab J. 2021;45(2):231-240.   Published online July 28, 2020
DOI: https://doi.org/10.4093/dmj.2019.0163
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Background

Most loci associated with type 2 diabetes mellitus (T2DM) discovered to date are within noncoding regions of unknown functional significance. By contrast, exonic regions have advantages for biological interpretation.

Methods

We analyzed the association of exome array data from 14,026 Koreans to identify susceptible exonic loci for T2DM. We used genotype information of 50,543 variants using the Illumina exome array platform.

Results

In total, 7 loci were significant with a Bonferroni adjusted P=1.03×10−6. rs2233580 in paired box gene 4 (PAX4) showed the highest odds ratio of 1.48 (P=1.60×10−10). rs11960799 in membrane associated ring-CH-type finger 3 (MARCH3) and rs75680863 in transcobalamin 2 (TCN2) were newly identified loci. When we built a model to predict the incidence of diabetes with the 7 loci and clinical variables, area under the curve (AUC) of the model improved significantly (AUC=0.72, P<0.05), but marginally in its magnitude, compared with the model using clinical variables (AUC=0.71, P<0.05). When we divided the entire population into three groups—normal body mass index (BMI; <25 kg/m2), overweight (25≤ BMI <30 kg/m2), and obese (BMI ≥30 kg/m2) individuals—the predictive performance of the 7 loci was greatest in the group of obese individuals, where the net reclassification improvement was highly significant (0.51; P=8.00×10−5).

Conclusion

We found exonic loci having a susceptibility for T2DM. We found that such genetic information is advantageous for predicting T2DM in a subgroup of obese individuals.

Citations

Citations to this article as recorded by  
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