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Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis.

ABSTRACT: Allergic rhinitis is a common disease whose genetic basis is incompletely explained. We report an integrated genomic analysis of allergic rhinitis.We performed genome wide association studies (GWAS) of allergic rhinitis in 5633 ethnically diverse North American subjects. Next, we profiled gene expression in disease-relevant tissue (peripheral blood CD4+ lymphocytes) collected from subjects who had been genotyped. We then integrated the GWAS and gene expression data using expression single nucleotide (eSNP), coexpression network, and pathway approaches to identify the biologic relevance of our GWAS.GWAS revealed ethnicity-specific findings, with 4 genome-wide significant loci among Latinos and 1 genome-wide significant locus in the GWAS meta-analysis across ethnic groups. To identify biologic context for these results, we constructed a coexpression network to define modules of genes with similar patterns of CD4+ gene expression (coexpression modules) that could serve as constructs of broader gene expression. 6 of the 22 GWAS loci with P-value???1x10-6 tagged one particular coexpression module (4.0-fold enrichment, P-value 0.0029), and this module also had the greatest enrichment (3.4-fold enrichment, P-value 2.6?×?10-24) for allergic rhinitis-associated eSNPs (genetic variants associated with both gene expression and allergic rhinitis). The integrated GWAS, coexpression network, and eSNP results therefore supported this coexpression module as an allergic rhinitis module. Pathway analysis revealed that the module was enriched for mitochondrial pathways (8.6-fold enrichment, P-value 4.5?×?10-72).Our results highlight mitochondrial pathways as a target for further investigation of allergic rhinitis mechanism and treatment. Our integrated approach can be applied to provide biologic context for GWAS of other diseases.

SUBMITTER: Bunyavanich S

PROVIDER: S-EPMC4127082 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis.

Bunyavanich Supinda S Schadt Eric E EE Himes Blanca E BE Lasky-Su Jessica J Qiu Weiliang W Lazarus Ross R Ziniti John P JP Cohain Ariella A Linderman Michael M Torgerson Dara G DG Eng Celeste S CS Pino-Yanes Maria M Padhukasahasram Badri B Yang James J JJ Mathias Rasika A RA Beaty Terri H TH Li Xingnan X Graves Penelope P Romieu Isabelle I Navarro Blanca del Rio Bdel R Salam M Towhid MT Vora Hita H Nicolae Dan L DL Ober Carole C Martinez Fernando D FD Bleecker Eugene R ER Meyers Deborah A DA Gauderman W James WJ Gilliland Frank F Burchard Esteban G EG Barnes Kathleen C KC Williams L Keoki LK London Stephanie J SJ Zhang Bin B Raby Benjamin A BA Weiss Scott T ST

BMC medical genomics 20140802

<h4>Background</h4>Allergic rhinitis is a common disease whose genetic basis is incompletely explained. We report an integrated genomic analysis of allergic rhinitis.<h4>Methods</h4>We performed genome wide association studies (GWAS) of allergic rhinitis in 5633 ethnically diverse North American subjects. Next, we profiled gene expression in disease-relevant tissue (peripheral blood CD4+ lymphocytes) collected from subjects who had been genotyped. We then integrated the GWAS and gene expression ...[more]

PMID: 25085501

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Dataset Information

Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis.

Publications

Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis.

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