Evidence for Genetic Susceptibility to Developing Early Childhood Diarrhea among Shantytown Children Living in Northeastern Brazil

Abstract

To explore the genetic components of susceptibility to early childhood diarrhea (ECD), we used a quantitative genetic approach to estimate the heritability of ECD among children from two Brazilian favelas. Shared environment was used to model common exposure to environmental factors. Genetic relatedness was determined from pedigree information collected by screening household participants (n = 3,267) from two geographically related favelas located in Fortaleza, Brazil. There were 277 children within these pedigrees for whom diarrheal episodes in the first two years of life were recorded. Data on environmental exposure and pedigree relationship were combined to quantitatively partition phenotypic variance in ECD into environmental and genetic components by using a variance components approach as implemented in Sequential Oligogenic Linkage Analysis Routines program. Heritability accounted for 54% of variance in ECD and proximity of residence effect accounted for 21% (P < 0.0001). These findings suggest a substantial genetic component to ECD susceptibility and the potential importance of future genetics studies.

A genome-wide association meta-analysis of diarrhoeal disease in young children identifiesFUT2locus and provides plausible biological pathways

“…Twin studies on infectious diseases have shown higher correlation between monozygotic than dizygotic twins (12)(13)(14). Heritability for early childhood diarrhoea was estimated to be 54% in a pedigreebased design in Brazil (15).…”

Apolipoprotein E Plays a Key Role against Cryptosporidial Infection in Transgenic Undernourished Mice

“…A reverberating vicious cycle of infection and malnutrition in young children may cause profound long-term deficits in physical and cognitive development, even without overt diarrhea, which can be irreversible [4] . The predisposition and adverse outcomes from repeated or prolonged exposure to C. parvum and other enteric infections may additionally have a strong genetic component in terms of host-parasite and epigenetic interactions [5] , [6] , which could affect the efficacy of nutritional interventions early in life in children at risk in endemic areas [7] and may have long-term consequences. Indeed, we have found that APOE4, the gene associated with increased susceptibility to Alzheimer's disease, is actually protective against early childhood diarrhea and its associated cognitive impairment [8] .…”

Blood is thicker than bloodshed: A genealogical approach to reconstruct populations after armed conflicts

“…Studies in population genetics often rely on a census-like approach for this. Genealogical data is collected from all households in a population and post-hoc efforts are made to merge the data and remove duplicates (Choh et al 2001;Pinkerton et al 2011). This procedure generally produces one big cluster of related individuals and several minor isolated genealogies, which are usually ignored for the analysis.…”