期刊
INFLAMMATORY BOWEL DISEASES
卷 21, 期 1, 页码 1-7出版社
OXFORD UNIV PRESS INC
DOI: 10.1097/MIB.0000000000000268
关键词
Crohn's disease; genetics; ImmunoChip; Korean
资金
- NRF (National Research Foundation of Korea) - Ministry of Science, Information & Communication Technology and Future Planning [2010-0015648, 2014R1 A2A1A09005824]
- Korean Health Technology R&D Project grant from the Ministry of Health & Welfare, the Republic of Korea [A120176]
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000124] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P01DK046763] Funding Source: NIH RePORTER
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 x 10(-11), odds ratio [OR] = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 x 10(-9), OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 x 10(-7), OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 x 10(-8), OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 x 10(-8), OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 x 10(-7), 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.
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