Robert O Wright1, David Christiani. 1. Department of Pediatrics, Children's Hospital, Harvard School of Public Health, Boston, Massachusetts, USA. rowright@hsph.harvard.edu
Abstract
PURPOSE OF REVIEW: A systematic approach to studying gene-environment interaction can have immediate impact on our understanding of how environmental factors induce developmental disease and toxicity and will provide biological insight for potential treatment and prevention measures. RECENT FINDINGS: Because DNA sequence is static, genetic studies typically are not conducted prospectively. This limits the ability to incorporate environmental data into an analysis, as such data is usually collected cross-sectionally. Prospective environmental data collection could account for the role of critical windows of susceptibility that likely correspond to the expression of specific genes and gene pathways. The use of large-scale genomic platforms to discover genetic variants that modify environmental exposure in conjunction with a-priori planned replication studies would reduce the number of false positive results. SUMMARY: Using a genome-wide approach, combined with prospective longitudinal measures of environmental exposure at critical developmental windows, is the optimal design for gene-environment interaction research. This approach would discover susceptibility variants, and then validate the findings in an independent sample of children. Designs that combine the strengths and methodologies of each field will yield data that can account for both genetic variability and the role of critical developmental windows in the etiology of childhood disease and development.
PURPOSE OF REVIEW: A systematic approach to studying gene-environment interaction can have immediate impact on our understanding of how environmental factors induce developmental disease and toxicity and will provide biological insight for potential treatment and prevention measures. RECENT FINDINGS: Because DNA sequence is static, genetic studies typically are not conducted prospectively. This limits the ability to incorporate environmental data into an analysis, as such data is usually collected cross-sectionally. Prospective environmental data collection could account for the role of critical windows of susceptibility that likely correspond to the expression of specific genes and gene pathways. The use of large-scale genomic platforms to discover genetic variants that modify environmental exposure in conjunction with a-priori planned replication studies would reduce the number of false positive results. SUMMARY: Using a genome-wide approach, combined with prospective longitudinal measures of environmental exposure at critical developmental windows, is the optimal design for gene-environment interaction research. This approach would discover susceptibility variants, and then validate the findings in an independent sample of children. Designs that combine the strengths and methodologies of each field will yield data that can account for both genetic variability and the role of critical developmental windows in the etiology of childhood disease and development.
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