Genome-wide association study of adenovirus-positive diarrhea in Bangladeshi infants

Adenovirus F40 and F41 are significant causes of acute gastroenteritis in infants, particularly in low-resource settings. Despite their clinical impact, the role of host genetics in susceptibility to these infections remains poorly understood. This study conducted a genome-wide association study (GWAS) using data from three independent birth cohorts in Dhaka, Bangladesh. The researchers compared 369 infants who experienced adenovirus-positive diarrhea in their first year of life against 285 infants who tested negative, aiming to identify genetic variants that influence susceptibility or resistance to the virus.

The meta-analysis identified three genome-wide significant loci associated with adenovirus-positive diarrhea:

• Chromosome 5 (rs7713577): Located near the MGAT1 gene, this variant was associated with increased risk of infection. It is also an expression quantitative trait locus (eQTL) for BTNL3 and SCGB3A1, genes involved in mucosal immune regulation.
• Chromosome 11 (rs4396295): Located in the 3' untranslated region of TESMIN, this variant was protective. It is linked to the expression of CPT1A, a mitochondrial enzyme critical for fatty acid oxidation, suggesting a potential immunometabolic role in resisting infection.
• Chromosome 12 (rs4269988): An intergenic variant upstream of TMEM132C, which has previously been implicated in susceptibility to enteric infections in other species.

These findings provide new insights into the biological pathways that govern how infants respond to enteric adenovirus. By identifying genes related to mucosal immunity and metabolic health, the study highlights potential host-directed therapeutic targets. Understanding these genetic factors could eventually lead to improved diagnostic tools or vaccines, helping to reduce the burden of severe diarrheal disease in vulnerable pediatric populations.