In:
Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 13, No. 5 ( 2019-04-26), p. 648-658
Abstract:
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 & lt;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.
Type of Medium:
Online Resource
ISSN:
1873-9946
,
1876-4479
DOI:
10.1093/ecco-jcc/jjy197
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2019
detail.hit.zdb_id:
2389631-0
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