Heritability of human hookworm infection in Papua New Guinea

Abstract

S U M M A R YHookworms infect approximately 740 million humans worldwide and are an important cause of morbidity. The present study examines the role of additive genetic effects in determining the intensity of hookworm infection in humans, and whether these effects vary according to the sex of the host. Parasitological and epidemiological data for a population of 704 subjects in Papua New Guinea were used in variance components analysis. The ' narrow-sense ' heritability of hookworm infection was estimated as 0 . 15¡0 . 04 (P<0 . 001), and remained significant when controlling for shared environmental (household) effects. Allowing the variance components to vary between the sexes of the human host consistently revealed larger additive genetic effects in females than in males, reflected by heritabilities of 0 . 18 in females and 0 . 08 in males in a conservative model. Household effects were also higher in females than males, although the overall household effect was not significant. The results indicate that additive genetic effects are an important determinant of the intensity of human hookworm infection in this population. However, despite similar mean and variance of intensity in each sex, the factors responsible for generating variation in intensity differ markedly between males and females.

Human helminth co-infection: No evidence of common genetic control of hookworm and Schistosoma mansoni infection intensity in a Brazilian community

“…Heritability estimates are population-specific, depending on the magnitude of both genetic and environmental variability; here, heritability is derived from a single large pedigree, which may result in lower genetic and/or environmental variance. However, our estimates are consistent with previous studies establishing a role for host genetics in determining infection burden for the major human STH (Williams-Blangero et al, ​1997, ​1999, 2002a; Breitling et al, 2008) and schistosome infections (Bethony et al, 2002; King et al, 2004; Seto et al, 2005; Ellis et al, 2006). Importantly, our results suggest that there is no, or very little, shared genetic control of N. americanus and S. mansoni infection intensity in this population, with a low and non-significant genetic correlation of 0.147.…”

Spatial and Genetic Epidemiology of Hookworm in a Rural Community in Uganda

“…Previous quantitative genetic analysis of helminth infection within human populations suggests roles for both extrinsic (domestic environmental) and intrinsic (genetic) factors in clustering of intestinal nematode infections within households [12], [14], [24], [25], [44], [45]. To date, the only study to investigate heritability in an African setting, conducted in Zimbabwe, suggested heritability of hookworm infection intensity was 0.37, although this study failed to account for household effects, limiting interpretation of findings.…”

“…Marked heterogeneity within communities has been long recognised for intestinal nematode infections [1], [10]–[12], [15], [18], [24]–[26], although there have been few studies undertaken in post-treatment settings in sub-Saharan Africa. This analysis sought to comprehensively assess major sources of heterogeneity (spatial, genetic and household) in the intensity of hookworm infection in a Ugandan population using both spatial and quantitative genetic modelling approaches.…”

“…Remarkably few investigations have been able to address spatial and/or genetic determinants of infection within African communities. However, our ability to investigate such factors today has been greatly facilitated by the increasing availability of high resolution spatial data and the advent of powerful analytical tools, including Geographic Information Systems (GIS), readily implemented Bayesian analysis and quantitative genetic approaches [8]–[12]. For example, GIS-based studies in a cohort of South African primary school children have demonstrated considerable spatial clustering of infection within a smaller area, strongly influenced by several environmental factors [10].…”

“…For example, GIS-based studies in a cohort of South African primary school children have demonstrated considerable spatial clustering of infection within a smaller area, strongly influenced by several environmental factors [10]. Similarly, several studies outside Africa have reported a significant role for both host genetics and the family environment in determining hookworm infection intensity [12]–[14], although the only genetic epidemiology investigation of hookworm in Africa did not account for the effects of shared family environment [15].…”