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Whole-exome sequencing study reveals common copy number variants in protocadherin genes associated with childhood obesity in Koreans

International Journal of Obesity volume 41, pages 660663 (2017) | Download Citation

Abstract

Recently, the prevalence of childhood obesity has significantly increased in industrialized countries, including Korea, and now controlling obesity is becoming an economic burden. However, knowledge of the risk factors associated with obesity is still limited. In this study, we aimed to discover additional obesity-associated loci in children. To achieve this, we conducted an exome-wide association analysis of copy number variation (CNV) using whole-exome sequencing (WES) data from a total of 102 cases and 86 controls. We newly identified a CNV locus that overlapped two protocadherin genes, PCDHB7 and PCDHB8, which are brain function-related genes (P-value=6.40 × 10−4, odds ratio=2.2189). A subsequent replication analysis using WES data from 203 obese and 291 normal weight children showed that this CNV region satisfied the genome-wide significance standard (Fisher’s combined P-value=3.76 × 10−5). Moreover, correlation test using 199 additional samples supported significant association between CNV and increased body mass index. This region also showed a meaningful association with 273 cases and 2596 controls in adult samples. Our findings suggest that differences in the common CNV region at 5q31.3 may have an impact on the pathophysiology of obesity.

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Acknowledgements

This work was supported by intramural grants from the Korea National Institute of Health (2012-N73004-00, 2014-NI73001-00, 2012-E64001-00). Data were also provided by the Korean Genome Analysis Project (4845-301) and the Korean Genome and Epidemiology Study (4851-302) that were supported by the Korea Center for Disease Control and Prevention, Republic of Korea.

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Affiliations

  1. Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea

    • S Moon
    • , M Y Hwang
    • , S Han
    • , Y J Kim
    • , J-Y Hwang
    •  & B-J Kim
  2. Division of Metabolic Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Republic of Korea

    • H B Jang
    • , H-J Lee
    • , S I Park
    •  & J Song

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The authors declare no conflict of interest.

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Correspondence to B-J Kim.

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DOI

https://doi.org/10.1038/ijo.2017.12

Supplementary Information accompanies this paper on International Journal of Obesity website (http://www.nature.com/ijo)