Metals such as manganese and arsenic are of increasing public health concern since recent data demonstrates their neurotoxicity to the developing brain. However, the role of genetic susceptibility to these toxic metals is unknown. Furthermore, while lead poisoning has been studied extensively, genetic susceptibility to its toxicity is not well understood. A systematic approach to studying gene-environment interaction would have immediate impact on our understanding of how metals induce toxicity and provide biological insight for potential treatment and prevention measures. In this project we will assess data from 3 cohort studies of metals and neurodevelopment. One in a developing country-Bangladesh, where metal exposures are unusually high, one in Mexico, a middle income country where metal exposures are moderately high, and one in a developed Country- (United States) in Tar Creek, OK, where exposure are representative of a community near a US toxic waste site. Tar Creek is a Superfund Megasite and former metal mining community. The success in assembling these cohorts has laid the groundwork for further research in genetic susceptibility to metals. Our 3 cohorts combined yield a sample of 2600 children with prospective data on metal exposure, and repeated neurophenotype measures;sufficient power to discover and to validate genetic susceptibility genes/SNPs. Using a genome-wide approach, we will discover susceptibility variants in a Discovery phase, and then Validate our findings in an independent sample of children while controlling for multiple comparisons. Furthermore, we will integrate with Project 3 (Genetic Mechanisms of Metal Neurotoxicity) to determine other biological pathways relevant to metal toxicity using state of the art siRNA technology to identify genes/pathways which promote/inhibit metal toxicity. This project represents perhaps the first large scale coordinated study of genetic susceptibility to metal toxicity and will provide biological insight into the mechanisms by which metals produce toxicity.
This project will clarify the relationship between exposure to metals such as arsenic, manganese and lead and childhood brain development In addition, we will examine the role of inherited (i.e., genetic) susceptibility on the metal-brain function relationship in children. The results of this project should help to guide preventive efforts aimed at children's environmental health.
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|Lee, Jane J; Valeri, Linda; Kapur, Kush et al. (2018) Growth parameters at birth mediate the relationship between prenatal manganese exposure and cognitive test scores among a cohort of 2- to 3-year-old Bangladeshi children. Int J Epidemiol 47:1169-1179|
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|von Stackelberg, Katherine; Li, Miling; Sunderland, Elsie (2017) Results of a national survey of high-frequency fish consumers in the United States. Environ Res 158:126-136|
|Valeri, Linda; Mazumdar, Maitreyi M; Bobb, Jennifer F et al. (2017) The Joint Effect of Prenatal Exposure to Metal Mixtures on Neurodevelopmental Outcomes at 20-40 Months of Age: Evidence from Rural Bangladesh. Environ Health Perspect 125:067015|
|Claus Henn, Birgit; Bellinger, David C; Hopkins, Marianne R et al. (2017) Maternal and Cord Blood Manganese Concentrations and Early Childhood Neurodevelopment among Residents near a Mining-Impacted Superfund Site. Environ Health Perspect 125:067020|
|Tamayo Y Ortiz, Marcela; Téllez-Rojo, Martha María; Trejo-Valdivia, Belem et al. (2017) Maternal stress modifies the effect of exposure to lead during pregnancy and 24-month old children's neurodevelopment. Environ Int 98:191-197|
|Lee, Jane J; Kapur, Kush; Rodrigues, Ema G et al. (2017) Anthropometric measures at birth and early childhood are associated with neurodevelopmental outcomes among Bangladeshi children aged 2-3years. Sci Total Environ 607-608:475-482|
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