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BMC Medical Genomics

, 7:48

Genomic epidemiology

Abstract

BackgroundAllergic rhinitis is a common disease whose genetic basis is incompletely explained. We report an integrated genomic analysis of allergic rhinitis.

MethodsWe 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.

ResultsGWAS 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 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 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.

ConclusionsOur 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.

KeywordsGenome-wide association study Allergic rhinitis Coexpression network Expression single-nucleotide polymorphism Coexpression module Pathway Mitochondria Hay fever Allergy AbbreviationsFDRFalse discovery rate

GWASGenome-wide association study

eQTLExpression quantitative trait loci

eSNPExpression single nucleotide polymorphism

GOGene ontology

IgEImmunoglobulin E

LDLinkage disequilibrium

QQQuantile quantile.

Electronic supplementary materialThe online version of this article doi:10.1186-1755-8794-7-48 contains supplementary material, which is available to authorized users.

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Author: Supinda Bunyavanich - Eric E Schadt - Blanca E Himes - Jessica Lasky-Su - Weiliang Qiu - Ross Lazarus - John P Ziniti -

Source: https://link.springer.com/







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