Genetic Susceptibility to Astrovirus Diarrhea in Bangladeshi Infants

Abstract

Astroviral infections commonly cause acute nonbacterial gastroenteritis in children globally. However, these infections often go undiagnosed outside of research settings. There is no treatment available for astrovirus, and Astroviridae strain diversity presents a challenge to potential vaccine development. To address our hypothesis that host genetic risk factors are associated with astrovirus disease susceptibility, we performed a genome-wide association study (GWAS) of astrovirus infection in the first year of life from children enrolled in two Bangladeshi birth cohorts. We identified a novel region on chromosome 1 near the loricrin gene (LOR) associated with astrovirus diarrheal infection (rs75437404, meta-analysis p-value=8.82x10-9, A allele OR=2.71) and on chromosome 10 near the prolactin releasing hormone receptor gene (PRLHR) (rs75935441, meta-analysis p-value=1.33x10-8, C allele OR=4.17). The prolactin-releasing peptide has been shown to influence feeding patterns and energy balance in mice. Additionally, several SNPs in the chromosome 1 locus have previously been associated with expression of innate immune system genes PGLYRP4, S100A9, and S100A12. This study identified two significant host genetic regions that may influence astrovirus diarrhea susceptibility and should be considered in further studies.