Theory and methods for mediation and interaction

项目摘要 拟议的研究将开发新的方法来评估遗传和基因之间的中介和相互作用。 环境暴露和不同的疾病亚型，以便更好地调整治疗和预防工作 以更好地了解控制疾病的机制。方法将 开发用于存在多种疾病亚型的环境，这些疾病亚型可能具有 不同的生存预后，可能更适合不同类型的治疗和预防 努力还将制定评估互动在理解机制方面的作用的方法。 这将包括阐明基因-环境相互作用在疾病遗传性中的作用， 了解在存在相互作用的情况下从暴露到疾病的介导途径，并确定 疾病或疾病亚型的充分原因相互作用，如果两种（或多种） 暴露是存在的，但如果只有一个或另一个存在。该方法将适用于 了解结直肠癌的预后，治疗决策，预防干预和机制， 以及皮肤病变的发展;该方法也将应用于了解 许多性状的遗传力的基因-环境交互作用。

Project Summary The proposed research will develop novel methods to assess mediation and interaction between genetic and environmental exposures and different disease subtypes so as to better tailor treatments and prevention efforts to individuals' characteristics and so as to better understand the mechanisms governing disease. Methods will be developed for settings in which there are multiple disease subtypes and these disease subtypes may have different prognosis for survival and may be more amenable to different types of treatment and preventive efforts. Methodology for assessing the role of interaction in understanding mechanisms will also be developed. This will include elucidating the role of gene-environment interaction in the heritability of disease, understanding mediating pathways from exposure to disease in the presence of interaction, and identifying sufficient cause interaction for diseases or disease subtypes such that an outcome would occur if two (or more) exposures are present, but not if only one or the other were present. The methodology will be applied to understand prognosis, treatment decisions, preventive interventions, and mechanisms for colorectal cancer, and also for the development of skin lesions; the methodology will also be applied to understand the role of gene-environment interaction in the heritability of numerous traits.