An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn’s Disease in Japanese Populations

Abstract

Expression quantitative trait locus (eQTL) analyses have enabled us to predict the function of disease susceptibility SNPs. However, eQTL for the effector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn’s disease (CD), are not yet available. Thus, we conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n = 20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confirmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed significant correlation with tenascin-XA (TNXA) expression were significantly associated with CD in GWAS. By TWAS, TNFSF15 (FDR = 1.35e-13) in whole blood, ERV3-1 (FDR = 2.18e-2) in lymphocytes, and ZNF713 (FDR = 3.04e-2) in the sigmoid colon was significantly associated with CD. By conducting integration analyses using GWAS and eQTL data, we confirmed multiple gene transcripts are involved in the development of CD.

Transcriptome‐wide profile of 1α,25 dihydroxyvitamin D3 in HTR‐8/SVneo cells

“…However, the effect of vitamin D on IL18R1 needs to be further confirmed. Only one study showed that ZNF713 was differentially expressed in the sigmoid colon of Crohn's disease by transcriptome sequencing, 49 which its function has not been investigated. According to zinc finger structure speculated that ZNF713 may play a role by regulating transcription.…”

A joint analysis using exome and transcriptome data identifies candidate polymorphisms and genes involved with umbilical hernia in pigs

“…Variants in the MYH8, MYH2, ENSSSCG00000036685 and MYO19 genes were identified only in the WES while variants in the ZNF713, ZNF629, ITGAM , SET1DA, RNF40, ORAI3, and ELOA were identified by the two methodologies. The zinc protein family genes identified in our study, such as ZNF629 and ZNF713, are associated with protein-protein interactions, with important role in the transcription and translation regulation [ 55 ] that have already been associated with bone and joint malformations, abnormalities of the skin, hair, teeth and nails [ 56 ]. Some zinc fingers have already been associated with other congenital diaphragmatic hernia [ 57 ].…”

Multi-omics in Crohn's disease: New insights from inside

“… CD-axSpA compared to HC, I3Ald ↑. Metabolomics 4 non-inflamed pinch biopsies of the distal colon LC-MS Kakuta, Yoichi et al 2020 [186] Genomics Genotyping data of 713 Japanese CD patients and 2063 controls GWAS 25 sites were confirmed as candidates correlated with Japanese CD by GWAS. 22,632 pairs in 2463 genes were confirmed to be candidates showing correlation between gene polymorphism and expression.…”