Department of Pediatrics, Children's Hospital, Harvard School of Public Health, Boston, Massachusetts, USA.
Curr Opin Pediatr. 2010 Apr;22(2):197-201. doi: 10.1097/MOP.0b013e328336ebf9.
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.
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.
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.
系统地研究基因-环境相互作用可以立即影响我们对环境因素如何诱导发育疾病和毒性的理解,并为潜在的治疗和预防措施提供生物学见解。
由于 DNA 序列是静态的,因此通常不会前瞻性地进行遗传研究。这限制了将环境数据纳入分析的能力,因为此类数据通常是横截面收集的。前瞻性环境数据收集可以说明易感性的关键窗口期的作用,这些窗口期可能与特定基因和基因途径的表达相对应。使用大规模基因组平台来发现可以改变特定基因和基因途径表达的关键发育窗口处环境暴露的遗传变异,并结合事先计划的复制研究,将减少假阳性结果的数量。
使用全基因组方法,结合关键发育窗口期前瞻性纵向的环境暴露测量,是研究基因-环境相互作用的最佳设计。这种方法将发现易感性变异,然后在儿童的独立样本中验证这些发现。结合每个领域的优势和方法的设计将产生既能解释遗传变异性又能说明关键发育窗口在儿童疾病和发育病因学中作用的数据。