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.
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, , Seoul, Korea.
authors.forename: Suk-Kyun
authors.initials: SK
authors.lastname: Yang
authors.forename: Myunghee
authors.initials: M
authors.lastname: Hong
authors.forename: Wanting
authors.initials: W
authors.lastname: Zhao
authors.forename: Yusun
authors.initials: Y
authors.lastname: Jung
authors.forename: Jiwon
authors.initials: J
authors.lastname: Baek
authors.forename: Naeimeh
authors.initials: N
authors.lastname: Tayebi
authors.forename: Kyung Mo
authors.initials: KM
authors.lastname: Kim
authors.forename: Byong Duk
authors.initials: BD
authors.lastname: Ye
authors.forename: Kyung-Jo
authors.initials: KJ
authors.lastname: Kim
authors.forename: Sang Hyoung
authors.initials: SH
authors.lastname: Park
authors.forename: Inchul
authors.initials: I
authors.lastname: Lee
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Byung Ik
authors.initials: BI
authors.lastname: Jang
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Jai Hyun
authors.initials: JH
authors.lastname: Choi
authors.forename: Ja Seol
authors.initials: JS
authors.lastname: Koo
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung-Ae
authors.initials: SA
authors.lastname: Jung
authors.forename: Yeoun Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Jang
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Hee-Shang
authors.initials: HS
authors.lastname: Youn
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Kyuyoung
authors.initials: K
authors.lastname: Song
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics*; D054637:Dual-Specificity Phosphatases / Q000235:genetics; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D000072260:RNA Splicing Factors; D056910:Republic of Korea; D055532:SMN Complex Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C479761:FCHSD2 protein, human; D020690:GTPase-Activating Proteins; D005819:Genetic Markers; C501168:KLF3 protein, human; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D000072260:RNA Splicing Factors; D055532:SMN Complex Proteins; C526478:SMNDC1 protein, human; C526441:TBC1D1 protein, human; C442320:DUSP5 protein, human; D054637:Dual-Specificity Phosphatases
keywords: Crohn's Disease; Genetic Polymorphisms; IBD – Genetics; Inflammatory Bowel Disease; Linkage Disequilibrium