Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations

Suk Kyun Yang, Myunghee Hong, Wanting Zhao, Yusun Jung, Jiwon Baek, Naeimeh Tayebi, Kyung Mo Kim, Byong Duk Ye, Kyung Jo Kim, Sang Hyoung Park, Inchul Lee, Eun Ju Lee, Won Ho Kim, Jae Hee Cheon, Young Ho Kim, Byung Ik Jang, Hyun Soo Kim, Jai Hyun Choi, Ja Seol Koo, Ji Hyun LeeSung Ae Jung, Yeoun Joo Lee, Joo Young Jang, Hyoung Doo Shin, Daehee Kang, Hee Shang Youn, Jianjun Liu, Kyuyoung Song

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106 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)80-87
Number of pages8
JournalGut
Volume63
Issue number1
DOIs
Publication statusPublished - 2014 Jan

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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    Yang, S. K., Hong, M., Zhao, W., Jung, Y., Baek, J., Tayebi, N., Kim, K. M., Ye, B. D., Kim, K. J., Park, S. H., Lee, I., Lee, E. J., Kim, W. H., Cheon, J. H., Kim, Y. H., Jang, B. I., Kim, H. S., Choi, J. H., Koo, J. S., ... Song, K. (2014). Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations. Gut, 63(1), 80-87. https://doi.org/10.1136/gutjnl-2013-305193