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

Research output: Contribution to journalArticle

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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 1

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Genome-Wide Association Study
Genetic Predisposition to Disease
Crohn Disease
Inflammatory Bowel Diseases
Population
Single Nucleotide Polymorphism
Validation Studies
Major Histocompatibility Complex
Genes
Meta-Analysis
Genome

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Yang, Suk Kyun ; Hong, Myunghee ; Zhao, Wanting ; Jung, Yusun ; Baek, Jiwon ; Tayebi, Naeimeh ; Kim, Kyung Mo ; Ye, Byong Duk ; Kim, Kyung Jo ; Park, Sang Hyoung ; Lee, Inchul ; Lee, Eun Ju ; Kim, Won Ho ; Cheon, Jae Hee ; Kim, Young Ho ; Jang, Byung Ik ; Kim, Hyun Soo ; Choi, Jai Hyun ; Koo, Ja Seol ; Lee, Ji Hyun ; Jung, Sung Ae ; Lee, Yeoun Joo ; Jang, Joo Young ; Shin, Hyoung Doo ; Kang, Daehee ; Youn, Hee Shang ; Liu, Jianjun ; Song, Kyuyoung. / Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations. In: Gut. 2014 ; Vol. 63, No. 1. pp. 80-87.
@article{f231ecd71d0c44e7a8bb4144cfff28d7,
title = "Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations",
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.",
author = "Yang, {Suk Kyun} and Myunghee Hong and Wanting Zhao and Yusun Jung and Jiwon Baek and Naeimeh Tayebi and Kim, {Kyung Mo} and Ye, {Byong Duk} and Kim, {Kyung Jo} and Park, {Sang Hyoung} and Inchul Lee and Lee, {Eun Ju} and Kim, {Won Ho} and Cheon, {Jae Hee} and Kim, {Young Ho} and Jang, {Byung Ik} and Kim, {Hyun Soo} and Choi, {Jai Hyun} and Koo, {Ja Seol} and Lee, {Ji Hyun} and Jung, {Sung Ae} and Lee, {Yeoun Joo} and Jang, {Joo Young} and Shin, {Hyoung Doo} and Daehee Kang and Youn, {Hee Shang} and Jianjun Liu and Kyuyoung Song",
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Yang, SK, Hong, M, Zhao, W, Jung, Y, Baek, J, Tayebi, N, Kim, KM, Ye, BD, Kim, KJ, Park, SH, Lee, I, Lee, EJ, Kim, WH, Cheon, JH, Kim, YH, Jang, BI, Kim, HS, Choi, JH, Koo, JS, Lee, JH, Jung, SA, Lee, YJ, Jang, JY, Shin, HD, Kang, D, Youn, HS, Liu, J & 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, vol. 63, no. 1, pp. 80-87. https://doi.org/10.1136/gutjnl-2013-305193

Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations. / Yang, Suk Kyun; Hong, Myunghee; Zhao, Wanting; Jung, Yusun; Baek, Jiwon; Tayebi, Naeimeh; Kim, Kyung Mo; Ye, Byong Duk; Kim, Kyung Jo; Park, Sang Hyoung; Lee, Inchul; Lee, Eun Ju; Kim, Won Ho; Cheon, Jae Hee; Kim, Young Ho; Jang, Byung Ik; Kim, Hyun Soo; Choi, Jai Hyun; Koo, Ja Seol; Lee, Ji Hyun; Jung, Sung Ae; Lee, Yeoun Joo; Jang, Joo Young; Shin, Hyoung Doo; Kang, Daehee; Youn, Hee Shang; Liu, Jianjun; Song, Kyuyoung.

In: Gut, Vol. 63, No. 1, 01.01.2014, p. 80-87.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations

AU - Yang, Suk Kyun

AU - Hong, Myunghee

AU - Zhao, Wanting

AU - Jung, Yusun

AU - Baek, Jiwon

AU - Tayebi, Naeimeh

AU - Kim, Kyung Mo

AU - Ye, Byong Duk

AU - Kim, Kyung Jo

AU - Park, Sang Hyoung

AU - Lee, Inchul

AU - Lee, Eun Ju

AU - Kim, Won Ho

AU - Cheon, Jae Hee

AU - Kim, Young Ho

AU - Jang, Byung Ik

AU - Kim, Hyun Soo

AU - Choi, Jai Hyun

AU - Koo, Ja Seol

AU - Lee, Ji Hyun

AU - Jung, Sung Ae

AU - Lee, Yeoun Joo

AU - Jang, Joo Young

AU - Shin, Hyoung Doo

AU - Kang, Daehee

AU - Youn, Hee Shang

AU - Liu, Jianjun

AU - Song, Kyuyoung

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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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