Daniel O'Connor (United Kingdom)
University of Oxford PaediatricsAuthor Of 1 Presentation
GENOMICS OF ALL-CAUSE PNEUMONIA AMONG NEPALESE CHILDREN
Abstract
Backgrounds:
Determining the key genomic characteristics of childhood pneumonia may inform the development of new clinical interventions for the disease. We used a genome-wide association study (GWAS) to identify variants associated with all-cause pneumonia and subsequently used these data to identify eQTL.
Methods
DNA and peripheral blood RNA were collected from healthy Nepalese children and Nepalese children admitted to Patan Hospital, Kathmandu with clinician diagnosed pneumonia. Samples were genotyped using Illumina Global Screening Arrays. Array data underwent QC and filtering before imputation using the HRC R1.1 2016 reference panel. Association analysis, by conducting a logistic regression using multidimensional scaling values, was performed using PLINK 2. RNA underwent whole-transcriptome sequencing using Illumina HiSeq4000, 75bp paired-end reads. Count data underwent filtering, normalisation, and batch correction, before eQTL were identified using MatrixeQTL.
Results:
A GWAS of 773 children with pneumonia (cases) and 2121 healthy community-based children (controls) identified rs79755386, proximal to B3GLT (involved in glycosylating o-linked mucins) to be associated with all-cause pneumonia (p=1.1x10-10, MAF cases = 0.09 vs MAF controls = 0.04, OR 2.3, 95% CI 1.8-2.9). Children with pneumonia who possessed the alternate allele, compared with those who had the reference, were more likely to have end-point consolidation on their chest x-ray (p=0.0492).
220 RNA samples from children with pneumonia were analysed. No cis eQTL were identified however, 230 significant trans eQTL to rs79755386 were identified with expression of HIC1 (p=8.9x10-5) which regulates T-cell differentiation, and SSH3 (p=0.0001) which plays a role in actin filament dynamics, having the most significant associations.
Conclusions/Learning Points:
rs79755386 is associated with childhood pneumonia and the expression of genes which likely affect both immune and respiratory epithelial function. Further examination of the role rs79755386 plays in respiratory epithelium function is required.