Ontology type: schema:ScholarlyArticle Open Access: True
2020-06-24
AUTHORSYoichi Kakuta, Ryo Ichikawa, Yuta Fuyuno, Atsushi Hirano, Junji Umeno, Takehiro Torisu, Kazuhiro Watanabe, Akihiro Asakura, Takeru Nakano, Yasuhiro Izumiyama, Daisuke Okamoto, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Takeshi Naito, Motohiro Esaki, Yosuke Kawai, Katsushi Tokunaga, Minoru Nakamura, Takayuki Matsumoto, Masao Nagasaki, Yoshitaka Kinouchi, Michiaki Unno, Atsushi Masamune
ABSTRACTExpression 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. More... »
PAGES10236
http://scigraph.springernature.com/pub.10.1038/s41598-020-66951-5
DOIhttp://dx.doi.org/10.1038/s41598-020-66951-5
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1128716710
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/32581322
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"description": "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\u2019s 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\u2009=\u200920). 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\u2009=\u20091.35e-13) in whole blood, ERV3-1 (FDR\u2009=\u20092.18e-2) in lymphocytes, and ZNF713 (FDR\u2009=\u20093.04e-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.",
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"name": "Scientific Reports",
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"keywords": [
"genome-wide association studies",
"eQTL analysis",
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"transcriptome-wide association study",
"association studies",
"expression quantitative trait loci (eQTL) analysis",
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"name": "An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn\u2019s Disease in Japanese Populations",
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