An investigation of expression quantitative trait loci in interferon genes in childhood asthma using RNA-sequencing data

Sneha P. Cherukuri | 2021

Advisor: Alison E. Fohner

Research Area(s): Clinical Epidemiology, Genetic Epidemiology, Maternal & Child Health

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Background: Asthma is the most common chronic disease among children and yet, many of the underlying mechanisms of severe disease remain poorly understood. Expression quantitative trait loci (eQTL) can provide mechanistic insight into the consequences of asthma risk variants and help explain variation in asthma severity. We identified and evaluated eQTLs in interferon molecular networks previously described in a transcriptome network analysis. Methods: This was a prospective cohort study with a high disease burden cohort consisting primarily of children from racial and ethnic minority populations. Sequenced RNA from nasal lavage samples were collected from 105 children diagnosed with asthma. Single-nucleotide polymorphisms (SNPs) from 6 interferon induced genes were assessed for Hardy-Weinberg equilibrium and used for cis-eQTL analysis after exclusions. Functional consequences of these SNPs were evaluated in genomic databases. Results: 5 SNPs from the IFI16, IFI44L, and IFIH1 genes were significantly associated (FDR<.05) with gene expression. 4 out of the 5 were described as missense variants, while 1 was described as a 3 prime untranslated region variant. Discussion: While 2 of the eQTLs from IFI16 were previously identified in the mucosa of the esophagus, we identified 3 novel airway epithelium eQTLs in IFI44L and IFIH1. Investigation of these genetic variants suggests they play a role in recognition of viruses and the prevention of viral infections, which may be crucial in efforts to prevent and treat viral asthma exacerbations.