Cargando…

Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a type of scarring lung disease characterized by a chronic, progressive, and irreversible decline in lung function. The genetic basis of IPF remains elusive. A transcriptome-wide association study (TWAS) of IPF was performed by FUSION using gene expression weig...

Descripción completa

Detalles Bibliográficos
Autores principales: Gong, Weiming, Guo, Ping, Liu, Lu, Guan, Qingbo, Yuan, Zhongshang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758323/
https://www.ncbi.nlm.nih.gov/pubmed/33362862
http://dx.doi.org/10.3389/fgene.2020.604324
_version_ 1783626917176410112
author Gong, Weiming
Guo, Ping
Liu, Lu
Guan, Qingbo
Yuan, Zhongshang
author_facet Gong, Weiming
Guo, Ping
Liu, Lu
Guan, Qingbo
Yuan, Zhongshang
author_sort Gong, Weiming
collection PubMed
description Idiopathic pulmonary fibrosis (IPF) is a type of scarring lung disease characterized by a chronic, progressive, and irreversible decline in lung function. The genetic basis of IPF remains elusive. A transcriptome-wide association study (TWAS) of IPF was performed by FUSION using gene expression weights of three tissues combined with a large-scale genome-wide association study (GWAS) dataset, totally involving 2,668 IPF cases and 8,591 controls. Significant genes identified by TWAS were then subjected to gene ontology (GO) and pathway enrichment analysis. The overlapped GO terms and pathways between enrichment analysis of TWAS significant genes and differentially expressed genes (DEGs) from the genome-wide mRNA expression profiling of IPF were also identified. For TWAS significant genes, protein–protein interaction (PPI) network and clustering modules analyses were further conducted using STRING and Cytoscape. Overall, TWAS identified a group of candidate genes for IPF under the Bonferroni corrected P value threshold (0.05/14929 = 3.35 × 10(–6)), such as DSP (P(TWAS) = 1.35 × 10(–29) for lung tissue), MUC5B (P(TWAS) = 1.09 × 10(–28) for lung tissue), and TOLLIP (P(TWAS) = 1.41 × 10(–15) for whole blood). Pathway enrichment analysis identified multiple candidate pathways, such as herpes simplex infection (P value = 7.93 × 10(–5)) and antigen processing and presentation (P value = 6.55 × 10(–5)). 38 common GO terms and 8 KEGG pathways shared by enrichment analysis of TWAS significant genes and DEGs were identified. In the PPI network, 14 genes (DYNLL1, DYNC1LI1, DYNLL2, HLA-DRB5, HLA-DPB1, HLA-DQB2, HLA-DQA2, HLA-DQB1, HLA-DRB1, POLR2L, CENPP, CENPK, NUP133, and NUP107) were simultaneously detected by hub gene and module analysis. In conclusion, through integrative analysis of TWAS and mRNA expression profiles, we identified multiple novel candidate genes, GO terms and pathways for IPF, which contributes to the understanding of the genetic mechanism of IPF.
format Online
Article
Text
id pubmed-7758323
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-77583232020-12-25 Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis Gong, Weiming Guo, Ping Liu, Lu Guan, Qingbo Yuan, Zhongshang Front Genet Genetics Idiopathic pulmonary fibrosis (IPF) is a type of scarring lung disease characterized by a chronic, progressive, and irreversible decline in lung function. The genetic basis of IPF remains elusive. A transcriptome-wide association study (TWAS) of IPF was performed by FUSION using gene expression weights of three tissues combined with a large-scale genome-wide association study (GWAS) dataset, totally involving 2,668 IPF cases and 8,591 controls. Significant genes identified by TWAS were then subjected to gene ontology (GO) and pathway enrichment analysis. The overlapped GO terms and pathways between enrichment analysis of TWAS significant genes and differentially expressed genes (DEGs) from the genome-wide mRNA expression profiling of IPF were also identified. For TWAS significant genes, protein–protein interaction (PPI) network and clustering modules analyses were further conducted using STRING and Cytoscape. Overall, TWAS identified a group of candidate genes for IPF under the Bonferroni corrected P value threshold (0.05/14929 = 3.35 × 10(–6)), such as DSP (P(TWAS) = 1.35 × 10(–29) for lung tissue), MUC5B (P(TWAS) = 1.09 × 10(–28) for lung tissue), and TOLLIP (P(TWAS) = 1.41 × 10(–15) for whole blood). Pathway enrichment analysis identified multiple candidate pathways, such as herpes simplex infection (P value = 7.93 × 10(–5)) and antigen processing and presentation (P value = 6.55 × 10(–5)). 38 common GO terms and 8 KEGG pathways shared by enrichment analysis of TWAS significant genes and DEGs were identified. In the PPI network, 14 genes (DYNLL1, DYNC1LI1, DYNLL2, HLA-DRB5, HLA-DPB1, HLA-DQB2, HLA-DQA2, HLA-DQB1, HLA-DRB1, POLR2L, CENPP, CENPK, NUP133, and NUP107) were simultaneously detected by hub gene and module analysis. In conclusion, through integrative analysis of TWAS and mRNA expression profiles, we identified multiple novel candidate genes, GO terms and pathways for IPF, which contributes to the understanding of the genetic mechanism of IPF. Frontiers Media S.A. 2020-12-10 /pmc/articles/PMC7758323/ /pubmed/33362862 http://dx.doi.org/10.3389/fgene.2020.604324 Text en Copyright © 2020 Gong, Guo, Liu, Guan and Yuan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Gong, Weiming
Guo, Ping
Liu, Lu
Guan, Qingbo
Yuan, Zhongshang
Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis
title Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis
title_full Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis
title_fullStr Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis
title_full_unstemmed Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis
title_short Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis
title_sort integrative analysis of transcriptome-wide association study and mrna expression profiles identifies candidate genes associated with idiopathic pulmonary fibrosis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758323/
https://www.ncbi.nlm.nih.gov/pubmed/33362862
http://dx.doi.org/10.3389/fgene.2020.604324
work_keys_str_mv AT gongweiming integrativeanalysisoftranscriptomewideassociationstudyandmrnaexpressionprofilesidentifiescandidategenesassociatedwithidiopathicpulmonaryfibrosis
AT guoping integrativeanalysisoftranscriptomewideassociationstudyandmrnaexpressionprofilesidentifiescandidategenesassociatedwithidiopathicpulmonaryfibrosis
AT liulu integrativeanalysisoftranscriptomewideassociationstudyandmrnaexpressionprofilesidentifiescandidategenesassociatedwithidiopathicpulmonaryfibrosis
AT guanqingbo integrativeanalysisoftranscriptomewideassociationstudyandmrnaexpressionprofilesidentifiescandidategenesassociatedwithidiopathicpulmonaryfibrosis
AT yuanzhongshang integrativeanalysisoftranscriptomewideassociationstudyandmrnaexpressionprofilesidentifiescandidategenesassociatedwithidiopathicpulmonaryfibrosis