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A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn's Disease in Japanese Individuals.


ABSTRACT: BACKGROUND AND AIMS:Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn's disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel. METHODS:Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions. RESULTS:Genotype data of 4?335?144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10-26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10-19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10-6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10-8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression. CONCLUSIONS:RAP1A is a novel susceptibility locus for CD in the Japanese population.

SUBMITTER: Kakuta Y 

PROVIDER: S-EPMC7458277 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn's Disease in Japanese Individuals.

Kakuta Yoichi Y   Kawai Yosuke Y   Naito Takeo T   Hirano Atsushi A   Umeno Junji J   Fuyuno Yuta Y   Liu Zhenqiu Z   Li Dalin D   Nakano Takeru T   Izumiyama Yasuhiro Y   Ichikawa Ryo R   Okamoto Daisuke D   Nagai Hiroshi H   Matsumoto Shin S   Yamamoto Katsutoshi K   Yokoyama Naonobu N   Chiba Hirofumi H   Shimoyama Yusuke Y   Onodera Motoyuki M   Moroi Rintaro R   Kuroha Masatake M   Kanazawa Yoshitake Y   Kimura Tomoya T   Shiga Hisashi H   Endo Katsuya K   Negoro Kenichi K   Yasuda Jun J   Esaki Motohiro M   Tokunaga Katsushi K   Nakamura Minoru M   Matsumoto Takayuki T   McGovern Dermot P B DPB   Nagasaki Masao M   Kinouchi Yoshitaka Y   Shimosegawa Tooru T   Masamune Atsushi A  

Journal of Crohn's & colitis 20190401 5


<h4>Background and aims</h4>Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn's disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel.<h4>Methods</h4>Two independent Japanese case/control sets  ...[more]

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