Dissecting the genetic contributions to fetal alcohol spectrum disorders

摘要 虽然胎儿酒精谱系障碍（FASD）需要产前酒精暴露，但很明显， 这种致畸性暴露的临床和身体表现有很大的变化。甚至儿童 产前酒精暴露相似的人会有完全不同的结果。据推测，其他因素， 其中一些可能是遗传性的，有助于这种变异。 FASD研究中的一个重大挑战是招募大量个体的能力， 以评估广泛的假设，并获得可推广到整个人口的结果。这 临床研究项目旨在通过实施创新的在线方法来应对这一挑战， 招募并同意一大批怀疑产前暴露于酒精的个体。这些 个人将有机会参加多个评估（唾液DNA，2D面部图像， 神经行为评估），这些评估将产生用于几项胎儿酒精合作计划的数据 疾病（CIFASD）项目。此外，被招募到这个在线队列中的个人可以被招募到 参与其他临床研究项目，包括作为CIFASD一部分的干预性研究。 从这个新的队列中在线获得的数据也将用于确定一个子集的个人与最 产前酒精暴露导致的极端表型来自目标研究受试者子集的DNA 将用于获得全外显子组测序，以有效地识别与以下相关的新风险和弹性因素： 产前酒精暴露的表型效应将共享结果并与CIFASD基础进行比较 利用动物模型确定风险因素的研究项目。 该临床研究项目与CIFASD高度整合，并与所有四种资源密切互动 以及多个临床和基础研究项目。

ABSTRACT While prenatal alcohol exposure is required for fetal alcohol spectrum disorders (FASD) it is clear that there is substantial variation in the clinical and physical manifestations of this teratogenic exposure. Even children with similar prenatal alcohol exposure can have quite different outcomes. It is hypothesized that other factors, some of which may be genetic, contribute to this variation. One of the significant challenges in studies of FASD is the ability to recruit large numbers of individuals in order to evaluate broad hypotheses and obtain results that are generalizable to the overall population. This clinical research project is designed to address this challenge by implementing innovative online approaches to recruit and consent a large cohort of individuals suspected to have been exposed to alcohol prenatally. These individuals will have the opportunity to participate in multiple assessments (saliva for DNA, 2D facial images, neurobehavioral assessments) that will generate data used in several Collaborative Initiative on Fetal Alcohol Disorders (CIFASD) projects. In addition, the individuals recruited into this online cohort can be recruited to participate in other clinical research projects, including interventional studies proposed as part of CIFASD. Data obtained online from this new cohort will also be used to identify a subset of individuals with the most extreme phenotypes resulting from prenatal alcohol exposure. DNA from a targeted subset of study subjects will be used to obtain whole exome sequencing to efficiently identify novel risk and resilience factors related to the phenotypic effects of prenatal alcohol exposure. Results will be shared and compared with CIFASD basic research projects utilizing animal models to identify risk factors. This clinical research project is highly integrated within CIFASD and interacts closely with all four resources as well as multiple clinical and basic research projects.