title: Immunochip analysis identification of 6 additional susceptibility loci for Crohn's disease in Koreans.
abstract: BACKGROUND
  Crohn's disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogether explain 5.31% of the risk for CD, the objective of this study was to identify additional CD susceptibility loci in the Korean population.
  
  
  METHODS
  Using the ImmunoChip custom single-nucleotide polymorphism array designed for dense genotyping of 186 loci identified through GWAS, we analyzed 722 individuals with CD and 461 controls for 96,048 SNP markers in the discovery stage, followed by validation in an additional 948 affected individuals and 977 controls.
  
  
  RESULTS
  We confirmed 6 previously reported loci in Caucasian: GPR35 at 2q37 (rs3749172; P = 5.30 × 10, odds ratio [OR] = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 × 10, OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 × 10, OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 × 10, OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 × 10, OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 × 10, OR = 1.35), bringing the number of known CD loci (including 3 in the HLA) in Koreans to 15. The 6 additional loci increased the total genetic variance for CD risk from 5.31% to 7.27% in Koreans.
  
  
  CONCLUSIONS
  Although the different genetic backgrounds of CD between Asian and Western countries has been well established for the major susceptibility genes, our findings of overlapping associations offer new insights into the genetic architecture of CD.
authors.affiliation: 1Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea; 3Human Genetics Group, Genome Institute of Singapore, Singapore, Singapore; 4The F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; 5Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 6Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; 7Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 8Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea; 9Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea; 10Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Ansan, Korea; 11Digestive Endoscopic Center, Seoul Song Do Colorectal Hospital, Seoul, Korea; 12Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea; 13Department of Life Science, Sogang University, Seoul, Korea; 14Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea; 15Department of Pediatrics, Gyeongsang National University School of Medicine, Jinju, Korea; and 16Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, and 17Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Suk-Kyun
authors.initials: SK
authors.lastname: Yang
authors.forename: Myunghee
authors.initials: M
authors.lastname: Hong
authors.forename: Hyunchul
authors.initials: H
authors.lastname: Choi
authors.forename: Wanting
authors.initials: W
authors.lastname: Zhao
authors.forename: Yusun
authors.initials: Y
authors.lastname: Jung
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
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: 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: 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: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Dermot P B
authors.initials: DP
authors.lastname: McGovern
authors.forename: Kyuyoung
authors.initials: K
authors.lastname: Song
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D015331:Cohort Studies; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D055815:Young Adult
chemical_list: D015415:Biomarkers