Immunochip Analysis Identification of 6 Additional Susceptibility Loci for Crohn's Disease in Koreans

被引：52

作者：

Yang, Suk-Kyun ^{[1
]}

Hong, Myunghee ^{[2
]}

Choi, Hyunchul ^{[2
]}

Zhao, Wanting ^{[3
]}

Jung, Yusun ^{[2
]}

Haritunians, Talin ^{[4
]}

Ye, Byong Duk ^{[1
]}

Kim, Kyung-Jo ^{[1
]}

Park, Sang Hyoung ^{[1
]}

Lee, Inchul ^{[5
]}

Kim, Won Ho ^{[6
]}

Cheon, Jae Hee ^{[6
]}

Kim, Young-Ho ^{[7
]}

Jang, Byung Ik ^{[8
]}

Kim, Hyun-Soo ^{[9
]}

Choi, Jai Hyun ^{[10
]}

Koo, Ja Seol ^{[10
]}

Lee, Ji Hyun ^{[11
]}

Jung, Sung-Ae ^{[12
]}

Shin, Hyoung Doo ^{[13
]}

Kang, Daehee ^{[14
]}

Youn, Hee-Shang ^{[15
]}

Taylor, Kent D. ^{[16
,17
]}

Rotter, Jerome I. ^{[16
,17
]}

Liu, Jianjun ^{[3
]}

McGovern, Dermot P. B. ^{[4
]}

Song, Kyuyoung ^{[2
]}

机构：

[1] Univ Ulsan, Coll Med, Dept Gastroenterol, Asan Med Ctr, Seoul 138736, South Korea

[2] Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, Seoul 138736, South Korea

[3] Genome Inst Singapore, Human Genet Grp, Singapore, Singapore

[4] Cedars Sinai Med Ctr, F Widjaja Fdn, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA

[5] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea

[6] Yonsei Univ, Coll Med, Dept Internal Med, Div Gastroenterol, Seoul, South Korea

[7] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Internal Med, Seoul, South Korea

[8] Yeungnam Univ, Coll Med, Dept Internal Med, Div Gastroenterol & Hepatol, Taegu, South Korea

[9] Yonsei Univ, Wonju Coll Med, Dept Internal Med, Wonju, South Korea

[10] Korea Univ, Coll Med, Inst Digest Dis & Nutr, Dept Internal Med, Ansan, South Korea

[11] Seoul Song Do Colorectal Hosp, Digest Endoscop Ctr, Seoul, South Korea

[12] Ewha Womans Univ, Sch Med, Dept Internal Med, Seoul, South Korea

[13] Sogang Univ, Dept Life Sci, Seoul, South Korea

[14] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea

[15] Gyeongsang Natl Univ, Sch Med, Dept Pediat, Jinju, South Korea

[16] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA

[17] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA

来源：

INFLAMMATORY BOWEL DISEASES | 2015年 / 21卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Crohn's disease; genetics; ImmunoChip; Korean; INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; JAPANESE PATIENTS; VARIANTS; POLYMORPHISMS; TNFSF15; GENE; ATG16L1; IL23R; EPIDEMIOLOGY;

D O I：

10.1097/MIB.0000000000000268

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：1 / 7

页数：7

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