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Genome-Wide Association Study of Ulcerative Colitis in Koreans Suggests Extensive Overlapping of Genetic Susceptibility With Caucasians

Yang, Suk-Kyun MD*; Hong, Myunghee MS; Zhao, Wanting PhD; Jung, Yusun PhD; Tayebi, Naeimeh MS; Ye, Byong Duk MD*; Kim, Kyung-Jo MD*; Park, Sang Hyoung MD*; Lee, Inchul MD§; Shin, Hyoung Doo PhD; Cheong, Hyun Sub PhD; Kim, Lyoung Hyo MS; Kim, Hyo-Jong MD**; Jung, Sung-Ae MD††; Kang, Daehee MD‡‡; Youn, Hee-Shang MD§§; Liu, Jianjun PhD; Song, Kyuyoung PhD

Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e3182802ab6
Original Basic Science Articles
Abstract

Background: Recent genome-wide association studies and meta-analyses have identified 47 susceptibility loci for ulcerative colitis (UC) in Caucasian populations. A previous genome-wide association study of UC in a Japanese population suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. We performed a genome-wide association studies to identify UC susceptibility loci in a Korean population and further comparative study.

Methods: We analyzed 581,060 autosomal single-nucleotide polymorphisms (SNPs) in 388 individuals with UC and 739 control subjects in the discovery stage. For the validation, 64 suggestive SNPs were analyzed in an additional 417 affected individuals and 732 control subjects.

Results: Three genetic loci were validated for significant association, and all were previously reported in Caucasians including the major histocompatibility complex region (top SNP, rs9271366; P = 1.03 × 10−18, odds ratio [OR] = 2.10), 16q24.1 (rs16940186; P = 4.39 × 10−10, OR = 1.56), and RNF186-OTUD3-PLA2G2E at chromosome arm 1p36.13 (top SNP, rs4654903 in OTUD3; P = 7.43 × 10−9, OR = 0.64). Although failed to reach genome-wide statistical significance, 2 additional loci previously reported in Caucasians including rs17085007 at chromosome arm 13q12 and JAK2 at chromosome arm 9p24 were significant after Bonferroni correction (Pcorrected = 0.0016 and Pcorrected = 0.0056, respectively). FOS, UBE2L3, the JAK2 gene region, and rs1297265 at chromosome arm 21q21.1 likely play a role in both Crohn’s disease and UC.

Conclusions: Our data support the biologic significance of the overlapping loci for UC between Caucasian and Korean populations. Our data suggest that genetic associations for UC tend to overlap more extensively among different ethnic groups than those for Crohn’s disease, which shows well-established dependence on ethnicity.

In Brief

Article first published online 18 March 2013

Author Information

*Department of Gastroenterology, Asan Medical Center;

Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea;

Human Genetics Group, Genome Institute of Singapore, Singapore;

§Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;

Department of Life Science, Sogang University, Seoul, South Korea;

Department of Genetic Epidemiology, SNP Genetics, Inc, Seoul, South Korea;

**Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, South Korea;

††Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, South Korea;

‡‡Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea; and

§§Department of Pediatrics, Gyeongsang National University School of Medicine, Jinju, South Korea.

Reprints: Kyuyoung Song, PhD, Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 88, Olympic-ro, 43-gil, Songpa-Gu, Seoul 138-736, Korea (e-mail: kysong@amc.seoul.kr).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).

Supported by Mid-career Researcher Program through National Research Foundation of Korea grant to K. Song (2010-0015648) funded by the Ministry of Education, Science and Technology, South Korea.

The authors have no conflict of interest to disclose.

S.-K. Yang, M. Hong, and W. Zhao contributed equally to this work.

Received July 11, 2012

Accepted July 27, 2012

© Crohn's & Colitis Foundation of America, Inc.

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