TY - JOUR
T1 - A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn's Disease in Japanese Individuals
AU - Kakuta, Yoichi
AU - Kawai, Yosuke
AU - Naito, Takeo
AU - Hirano, Atsushi
AU - Umeno, Junji
AU - Fuyuno, Yuta
AU - Liu, Zhenqiu
AU - Li, Dalin
AU - Nakano, Takeru
AU - Izumiyama, Yasuhiro
AU - Ichikawa, Ryo
AU - Okamoto, Daisuke
AU - Nagai, Hiroshi
AU - Matsumoto, Shin
AU - Yamamoto, Katsutoshi
AU - Yokoyama, Naonobu
AU - Chiba, Hirofumi
AU - Shimoyama, Yusuke
AU - Onodera, Motoyuki
AU - Moroi, Rintaro
AU - Kuroha, Masatake
AU - Kanazawa, Yoshitake
AU - Kimura, Tomoya
AU - Shiga, Hisashi
AU - Endo, Katsuya
AU - Negoro, Kenichi
AU - Yasuda, Jun
AU - Esaki, Motohiro
AU - Tokunaga, Katsushi
AU - Nakamura, Minoru
AU - Matsumoto, Takayuki
AU - McGovern, Dermot P.B.
AU - Nagasaki, Masao
AU - Kinouchi, Yoshitaka
AU - Shimosegawa, Tooru
AU - Masamune, Atsushi
N1 - Publisher Copyright:
Copyright © 2018 European Crohn's and Colitis Organisation (ECCO).
PY - 2019/4/26
Y1 - 2019/4/26
N2 - 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.
AB - 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.
KW - Crohn's disease
KW - RAP1A
KW - susceptibility gene
UR - http://www.scopus.com/inward/record.url?scp=85068490457&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068490457&partnerID=8YFLogxK
U2 - 10.1093/ecco-jcc/jjy197
DO - 10.1093/ecco-jcc/jjy197
M3 - Article
C2 - 30500874
AN - SCOPUS:85068490457
SN - 1873-9946
VL - 13
SP - 648
EP - 658
JO - Journal of Crohn's and Colitis
JF - Journal of Crohn's and Colitis
IS - 5
ER -