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Genetic Susceptibility to Astrovirus Diarrhea in Bangladeshi Infants
Laura Chen1, Rebecca M Munday2, Rashidul Haque3
1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Insights
Researchers identified two key genetic regions linked to astrovirus diarrhea susceptibility in infants. This discovery could inform future studies on preventing childhood gastroenteritis and developing astrovirus treatments.
Area of Science:
- Genetics
- Infectious Diseases
- Pediatrics
Background:
- Astroviral infections cause widespread gastroenteritis in children but are often undiagnosed.
- Current lack of astrovirus treatment and vaccine challenges due to strain diversity.
Purpose of the Study:
- Investigate host genetic factors influencing susceptibility to astrovirus infection.
- Identify specific genetic risk factors for astrovirus disease in early childhood.
Main Methods:
- Conducted a genome-wide association study (GWAS) in two Bangladeshi birth cohorts.
- Analyzed astrovirus infection data from children within their first year of life.
Main Results:
- Identified a novel genetic region on chromosome 1 near the loricrin gene (LOR) associated with astrovirus diarrhea (rs75437404).
- Discovered another significant region on chromosome 10 near the prolactin releasing hormone receptor gene (PRLHR) (rs75935441).
- Found associations between single-nucleotide polymorphisms and innate immune gene expression.
Conclusions:
- Two significant host genetic regions potentially influence astrovirus diarrhea susceptibility.
- These findings warrant further investigation into host genetics and astrovirus disease.
Background:
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.
Methods:
To address our hypothesis that host genetic risk factors are associated with astrovirus disease susceptibility, we performed a genome-wide association study of astrovirus infection in the first year of life from children enrolled in 2 Bangladeshi birth cohorts.
Results:
We identified a novel region on chromosome 1 near the loricrin gene (LOR) associated with astrovirus diarrheal infection (rs75437404; meta-analysis P = 8.82 × 10-9; A allele odds ratio, 2.71) and on chromosome 10 near the prolactin releasing hormone receptor gene (PRLHR) (rs75935441; meta-analysis P = 1.33 × 10-8; C allele odds ratio, 4.17). The prolactin-releasing peptide has been shown to influence feeding patterns and energy balance in mice. In addition, several single-nucleotide polymorphisms in the chromosome 1 locus have previously been associated with expression of innate immune system genes PGLYRP4, S100A9, and S100A12.
Conclusions:
This study identified 2 significant host genetic regions that may influence astrovirus diarrhea susceptibility and should be considered in further studies.
