Immunochip analysis identification of 6 additional susceptibility loci for Crohn's disease in Koreans

Suk Kyun Yang, Myunghee Hong, Hyunchul Choi, Wanting Zhao, Yusun Jung, Talin Haritunians, Byong Duk Ye, Kyung Jo Kim, Sang Hyoung Park, Inchul Lee, Won Ho Kim, Jae Hee Cheon, Young Ho Kim, Byung Ik Jang, Hyun Soo Kim, Jai Hyun Choi, Ja Seol Koo, Ji Hyun Lee, Sung Ae Jung, Hyoung Doo ShinDaehee Kang, Hee Shang Youn, Kent D. Taylor, Jerome I. Rotter, Jianjun Liu, Dermot P.B. McGovern, Kyuyoung Song

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Crohn's disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogether explain 5.31% of the risk for CD, the objective of this study was to identify additional CD susceptibility loci in the Korean population. Methods: Using the ImmunoChip custom single-nucleotide polymorphism array designed for dense genotyping of 186 loci identified through GWAS, we analyzed 722 individuals with CD and 461 controls for 96,048 SNP markers in the discovery stage, followed by validation in an additional 948 affected individuals and 977 controls. Results: We confirmed 6 previously reported loci in Caucasian: GPR35 at 2q37 (rs3749172; P = 5.30 • 10-11, odds ratio [OR] = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 • 10-9, OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 • 10-7, OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 • 10-8, OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 • 10-8, OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 • 10-7, OR = 1.35), bringing the number of known CD loci (including 3 in the HLA) in Koreans to 15. The 6 additional loci increased the total genetic variance for CD risk from 5.31% to 7.27% in Koreans. Conclusions: Although the different genetic backgrounds of CD between Asian and Western countries has been well established for the major susceptibility genes, our findings of overlapping associations offer new insights into the genetic architecture of CD.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalInflammatory Bowel Diseases
Volume21
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

Keywords

  • Crohn's disease
  • Genetics
  • ImmunoChip
  • Korean

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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    Yang, S. K., Hong, M., Choi, H., Zhao, W., Jung, Y., Haritunians, T., Ye, B. D., Kim, K. J., Park, S. H., Lee, I., Kim, W. H., Cheon, J. H., Kim, Y. H., Jang, B. I., Kim, H. S., Choi, J. H., Koo, J. S., Lee, J. H., Jung, S. A., ... Song, K. (2015). Immunochip analysis identification of 6 additional susceptibility loci for Crohn's disease in Koreans. Inflammatory Bowel Diseases, 21(1), 1-7. https://doi.org/10.1097/MIB.0000000000000268