Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, Jha P, Campbell H, Walker CF, Cibulskis R, Eisele T, Liu L, Mathers C; Child Health Epidemiology Reference Group Of WHO and UNICEF, 2010. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 375: 1969–1987.
Kosek M, Bern C, Guerrant RL, 2003. The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ 81: 197–204.
Moore SR, Lima AA, Conaway MR, Schorling JB, Soares AM, Guerrant RL, 2001. Early childhood diarrhoea and helminthiases associate with long-term linear growth faltering. Int J Epidemiol 30: 1457–1464.
Checkley W, Buckley G, Gilman RH, Assis AM, Guerrant RL, Morris SS, Molbak K, Valentiner-Branth P, Lanata CF, Black RE, 2008. Multi-country analysis of the effects of diarrhea on childhood stunting. Int J Epidemiol 37: 816–830.
Guerrant DI, Moore SR, Lima AA, Patrick PD, Schorling JB, Guerrant RL, 1999. Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil. Am J Trop Med Hyg 61: 707–713.
Guerrant RL, Oria RB, Moore SR, Oria MO, Lima AA, 2008. Malnutrition as an enteric infectious disease with long-term effects on child development. Nutr Rev 66: 487–505.
Cheng AC, McDonald JR, Thielman NM, 2005. Infectious diarrhea in developed and developing countries. J Clin Gastroenterol 39: 757–773.
Steiner TS, Samie A, Guerrant RL, 2006. Infectious diarrhea: new pathogens and new challenges in developed and developing areas. Clin Infect Dis 43: 408–410.
Williams-Blangero S, Vandeberg JL, Subedi J, Jha B, Correa-Oliveira R, Blangero J, 2008. Localization of multiple quantitative trait loci influencing susceptibility to infection with Ascaris lumbricoides. J Infect Dis 197: 66–71.
Ramsay CE, Hayden CM, Tiller KJ, Burton PR, Goldblatt J, Lesouef PN, 1999. Polymorphisms in the beta2-adrenoreceptor gene are associated with decreased airway responsiveness. Clin Exp Allergy 29: 1195–1203.
Peisong G, Yamasaki A, Mao XQ, Enomoto T, Feng Z, Gloria-Bottini F, Bottini E, Shirakawa T, Sun D, Hopkin JM, 2004. An asthma-associated genetiv variant of STAT6 predicts low burden of Ascaris worm infestation. Genes Immun 5: 58–62.
Kirkpatrick BD, Haque R, Duggal P, Mondal D, Larsson C, Peterson K, Akter J, Lockhart L, Khan S, Petri WA Jr, 2008. Associations between Cryptosporidium infections and human leukocyte antigen class I and class II alleles. J Infect Dis 197: 474–478.
Duggal P, Haque R, Roy S, Mondal D, Sack RB, Farr BM, Beaty TH, Petri WA Jr, 2004. Influence of human leukocyte antigen class II alleles on susceptibility to Entamoeba histolytica infection in Bangladeshi children. J Infect Dis 189: 520–526.
Duggal P, Guo X, Haque R, Peterson KM, Ricklefs S, Mondal D, Alam F, Noor Z, Verkerke HP, Marie C, Leduc CA, Chua SC Jr., Myers MJ Jr, Leibel SR, Houpt E, Gilchrist CA, Sher A, Porcella SF, Petri WA Jr. 2011. A mutation in the leptin receptor is associated with Entamoeba histolytica infection in chioldren. J Clin Invest 121: 1191–1198.
Williams-Blangero S, Blangero J, 2006. Collection of pedigree data for genetic analysis in isolate populations. Hum Biol 78: 89–101.
Dillingham R, Guerrant RL, 2004. Childhood stunting: measuring and stemming the staggering costs of inadequate water and sanitation. Lancet 363: 94–95.
Copeland CC, Beers BB, Thompson MR, Fitzgerald RP, Barrett LJ, Sevilleja JE, Alencar S, Lima AA, Guerrant RL, 2009. Faecal contamination of drinking water in a Brazilian shanty town: importance of household storage and new human faecal marker testing. J Water Health 7: 324–331.
Lima AA, Moore SR, Barboza MS Jr, Soares AM, Schleupner MA, Newman RD, Sears CL, Nataro JP, Fedorko DP, Wuhib T, Schorling JB, Guerrant RL, 2000. Persistent diarrhea signals a critical period of increased diarrhea burdens and nutritional shortfalls: a prospective cohort study among children in northeastern Brazil. J Infect Dis 181: 1643–1651.
Lima AA, Guerrant RL, 1992. Persistent diarrhea in children: epidemiology, risk factors, pathophysiology, nutritional impact, and management. Epidemiol Rev 14: 222–242.
Steiner TS, Lima AA, Nataro JP, Guerrant RL, 1998. Enteroaggregative Escherichia coli produce intestinal inflammation and growth impairment and cause interleukin-8 release from intestinal epithelial cells. J Infect Dis 177: 88–96.
Jiang ZD, Okhuysen PC, Guo DC, He R, King TM, DuPont HL, Milewicz DM, 2003. Genetic susceptibility to enteroaggregative Escherichia coli diarrhea: polymorphism in the interleukin-8 promotor region. J Infect Dis 188: 506–511.
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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.
Financial support: This study was supported in part by the National Institute of Allergy and Infectious Disease ICIDR grant U01A1026512, Support was also provided by Global Infectious Disease Research Training grant D43 TW006578.
Authors' addresses: Relana C. Pinkerton, Anita Kohli, and Oluma Bushen, University of Virginia Center for Global Health, Charlottesville, VA. Reinaldo B. Oriá and Claudia Abreu, Institute of Biomedicine and Department of Morphology, School of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil. Jack W. Kent Jr., John Blangero, and Sarah Williams-Blangero, Texas Biomedical Research Institute, San Antonio, TX. Aldo A. M. Lima and Richard L. Guerrant, University of Virginia Center for Global Health, Charlottesville, VA, and Institute of Biomedicine and Department of Morphology, School of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil.