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Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations
  1. Suk-Kyun Yang1,
  2. Myunghee Hong2,
  3. Wanting Zhao3,
  4. Yusun Jung2,
  5. Jiwon Baek2,
  6. Naeimeh Tayebi3,
  7. Kyung Mo Kim4,
  8. Byong Duk Ye1,
  9. Kyung-Jo Kim1,
  10. Sang Hyoung Park1,
  11. Inchul Lee5,
  12. Eun-Ju Lee2,
  13. Won Ho Kim6,
  14. Jae Hee Cheon6,
  15. Young-Ho Kim7,
  16. Byung Ik Jang8,
  17. Hyun-Soo Kim9,
  18. Jai Hyun Choi10,
  19. Ja Seol Koo10,
  20. Ji Hyun Lee11,
  21. Sung-Ae Jung12,
  22. Yeoun Joo Lee4,
  23. Joo Young Jang13,
  24. Hyoung Doo Shin14,
  25. Daehee Kang15,
  26. Hee-Shang Youn16,
  27. Jianjun Liu3,
  28. Kyuyoung Song2
  1. 1Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  2. 2Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea
  3. 3Human Genetics Group, Genome Institute of Singapore, Singapore, Singapore
  4. 4Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
  5. 5Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  6. 6Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
  7. 7Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  8. 8Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
  9. 9Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
  10. 10Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Ansan, Korea
  11. 11Digestive Endoscopic Center, Seoul Song Do Colorectal Hospital, Seoul, Korea
  12. 12Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
  13. 13Department of Pediatrics, Ajou University School of Medicine, Suwon, Korea
  14. 14Department of Life Science, Sogang University, Seoul, Korea
  15. 15Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
  16. 16Department of Pediatrics, Gyeongsang National University School of Medicine, Jinju, Korea
  1. Correspondence to Professor Kyuyoung Song, Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 88, Olympic-ro, 43-gil, Songpa-Gu, Seoul 138-736, Korea; kysong{at}amc.seoul.kr

Abstract

Objective Crohn's disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified 163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations.

Methods We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls.

Results We confirmed four previously reported loci: TNFSF15, IL23R, the major histocompatibility complex region, and the RNASET2-FGFR1OP-CCR6 region. We identified three new susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43, combined p=3.60×10−14), rs11195128 at 10q25 (OR=1.42, combined p=1.55×10−10) and rs11235667 at 11q13 (OR=1.46, combined p=7.15×10−9), implicating ATG16L2 and/or FCHSD2 as novel susceptibility genes for CD. Further analysis of the 11q13 locus revealed a non-synonymous single nucleotide polymorphism (SNP) (R220W/rs11235604) in the evolutionarily conserved region of ATG16L2 with stronger association (OR=1.61, combined p=2.44×10−12) than rs11235667, suggesting ATG16L2 as a novel susceptibility gene for CD and rs11235604 to be a potential causal variant of the association. Two of the three SNPs (rs6856616 (p=0.00024) and rs11195128 (p=5.32×10−5)) showed consistent patterns of association in the International IBD Genetics Consortium dataset. Together, the novel and replicated loci accounted for 5.31% of the total genetic variance for CD risk in Koreans.

Conclusions Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.

  • Crohn's Disease
  • Genetic Polymorphisms
  • IBD – Genetics
  • Linkage Disequilibrium
  • Inflammatory Bowel Disease

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