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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
Open accessAbstract
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.
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Metadata
- Authors
- 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., Lee, J. H., Jung, S.-A., Lee, Y. J., Jang, J. Y., Shin, H. D., Kang, D., Youn, H.-S., Liu, J., & Song, K.
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2013-07-14
- Volume
- 63
- Issue
- 1
- Pages
- 80-87
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2158132545
- Cited by
- 184
- References
- 9
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- green
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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. https://doi.org/10.1136/gutjnl-2013-305193
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