Genome-Wide Association Studies of Diarrhea Frequency and Duration in the First Year of Life in Bangladeshi Infants

Background. Diarrhea is the second leading cause of death in children under 5 years old worldwide. Known diarrhea risk factors include sanitation, water sources, and pathogens but do not fully explain the heterogeneity in frequency and duration of diarrhea in young children. We evaluated the role of host genetics in diarrhea. Methods. Using 3 well-characterized birth cohorts from an impoverished area of Dhaka, Bangladesh, we compared infants with no diarrhea in the first year of life to those with an abundance, measured by either frequency or duration. We performed a genome-wide association analysis for each cohort under an additive model and then meta-analyzed across the studies. Results. For diarrhea frequency, we identified 2 genome-wide significant loci associated with not having any diarrhea, on chromosome 21 within the noncoding RNA AP000959 (C allele odds ratio [OR] = 0.31, P = 4.01 x 10(-8)), and on chromosome 8 within SAMD12 (T allele OR = 0.35, P = 4.74 x 10(-7)). For duration of diarrhea, we identified 2 loci associated with no diarrhea, including the same locus on chromosome 21 (C allele OR = 0.31, P = 1.59 x 10(-8)) and another locus on chromosome 17 near WSCD1 (C allele OR = 0.35, P = 1.09 x 10(-7)). Conclusions. These loci are in or near genes involved in enteric nervous system development and intestinal inflammation and may be potential targets for diarrhea therapeutics.