Host Genome-Wide Association Study of Infant Susceptibility to Shigella-Associated Diarrhea [Host Response and Inflammation]

Shigella is a leading cause of moderate-to-severe diarrhea globally and the causative agent of shigellosis and bacillary dysentery. Associated with 80 to 165 million cases of diarrhea and >13% of diarrheal deaths, in many regions, Shigella exposure is ubiquitous while infection is heterogenous. To characterize host-genetic susceptibility to Shigella-associated diarrhea, we performed two independent genome-wide association studies (GWAS) including Bangladeshi infants from the PROVIDE and CBC birth cohorts in Dhaka, Bangladesh. Cases were infants with Shigella-associated diarrhea (n = 143) and controls were infants with no Shigella-associated diarrhea in the first 13 months of life (n = 446). Shigella-associated diarrhea was identified via quantitative PCR (qPCR) threshold cycle (CT) distributions for the ipaH gene, carried by all four Shigella species and enteroinvasive Escherichia coli. Host GWAS were performed under an additive genetic model. A joint analysis identified protective loci on chromosomes 11 (rs582240, within the KRT18P59 pseudogene; P = 6.40 x 10–8; odds ratio [OR], 0.43) and 8 (rs12550437, within the lincRNA RP11-115J16.1; P = 1.49 x 10–7; OR, 0.48). Conditional analyses identified two previously suggestive loci, a protective locus on chromosome 7 (rs10266841, within the 3' untranslated region [UTR] of CYTH3; Pconditional = 1.48 x 10–7; OR, 0.44) and a risk-associated locus on chromosome 10 (rs2801847, an intronic variant within MPP7; Pcond...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research