免疫芯片分析在韩国人中鉴定出另外6个克罗恩病易感基因座。
Immunochip analysis identification of 6 additional susceptibility loci for Crohn's disease in Koreans.
作者信息
Yang Suk-Kyun, Hong Myunghee, Choi Hyunchul, Zhao Wanting, Jung Yusun, Haritunians Talin, Ye Byong Duk, Kim Kyung-Jo, Park Sang Hyoung, Lee Inchul, 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, Shin Hyoung Doo, Kang Daehee, Youn Hee-Shang, Taylor Kent D, Rotter Jerome I, Liu Jianjun, McGovern Dermot P B, Song Kyuyoung
机构信息
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.
出版信息
Inflamm Bowel Dis. 2015 Jan;21(1):1-7. doi: 10.1097/MIB.0000000000000268.
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.
背景
克罗恩病（CD）是一种病因不明的难治性炎症性肠病。最近在韩国和日本人群中进行的CD全基因组关联研究表明，白种人和亚洲人群之间的易感基因座存在少量共享。由于已确定的7个基因座总共解释了5.31%的CD发病风险，本研究的目的是在韩国人群中鉴定其他CD易感基因座。
方法
使用专为通过全基因组关联研究（GWAS）确定的186个基因座进行密集基因分型而设计的免疫芯片定制单核苷酸多态性阵列，我们在发现阶段对722例CD患者和461例对照进行了96,048个单核苷酸多态性（SNP）标记的分析，随后在另外948例受累个体和977例对照中进行了验证。
结果
我们在白种人中确认了6个先前报道的基因座：位于2q37的GPR35（rs3749172；P = 5.30×10，优势比[OR] = 1.45）、位于10q21的ZNF365（rs224143；P = 2.20×10，OR = 1.38）、位于10q22的ZMIZ1（rs1250569；P = 3.05×10，OR = 1.30）、位于10q24的NKX2 - 3（rs4409764；P = 7.93×10，OR = 1.32）、位于18p11的PTPN2（rs514000；P = 9.00×10，OR = 1.33）以及位于21q11的USP25（rs2823256；P = 2.49×10，OR = 1.35），这使得韩国人中已知的CD基因座（包括HLA中的3个）数量增加到15个。这6个额外的基因座将韩国人中CD风险的总遗传变异从5.31%提高到了7.27%。
结论
尽管亚洲和西方国家之间CD的不同遗传背景在主要易感基因方面已得到充分证实，但我们关于重叠关联的发现为CD的遗传结构提供了新的见解。
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