A Twin Study of Autism Spectrum Disorder

描述(由申请人提供)：这项申请寻求五年的支持，以进行第一个以人群为基础的自闭症谱系障碍(ASD)双胞胎研究，病例使用当前的诊断标准确定。关于基因对自闭症影响程度的推断主要取决于同卵双胞胎(MZ)和同卵异卵双胞胎(DZ)的差异一致性。双胞胎研究的结果影响了各种连锁方法的可信程度。诊断实践的改变导致了基本比率和双胞胎先证者识别的差异，因此需要新的研究。此外，需要对双胞胎进行基于人群的研究，以调查双胞胎在自闭症病例中比例过高的说法。 在确定该项目可行性的大量数据的基础上，我们将收集威斯康星州几乎所有2-16岁双胞胎的样本，首先通过筛查和病例发现，然后通过进行全面的诊断和行为评估。我们预测了120对双胞胎的最终样本，其中一对或两对都患有自闭症；大约80%的病例应该是特发性的。鉴于我们的目标是量化ASD的遗传贡献，我们还将评估家庭成员中更广泛的自闭症表型。我们将描述共同发生的但非诊断性的行为问题(焦虑、运动障碍、感官敏感、睡眠问题、攻击性或自残行为)以及其他医疗条件。将评估家庭功能，以了解自闭症的影响，并将监测对治疗的反应，以利于未来的转化研究。纵向随访将允许确认早期诊断和测量ASD的病程。一项神经成像研究，包括眼睛跟踪和皮肤电测量，将在8岁以上的双胞胎亚样本上进行，特别关注不和谐的MZ对。

DESCRIPTION (provided by applicant): This application seeks five years of support to conduct the first population-based twin study of autism spectrum disorder (ASD) with cases ascertained using current day diagnostic criteria. Inferences about the degree of genetic influence on autism depend crucially on the differential concordance of monozygotic (MZ) vs. dizygotic (DZ) cotwins. The results of twin studies affect the plausibility of various linkage approaches. Changing diagnostic practices lead to differences in base rates and in twin proband identification and thus require new studies. In addition, population-based studies of twins are needed to investigate claims that twins are over-represented among ASD cases. Building on extensive data that establish the project's feasibility, we shall collect a sample of virtually all twins aged 2-16 years in the state of Wisconsin, first by screening and case-finding, then by performing full diagnostic and behavioral assessments. We project a final sample of >120 pairs of twins, one or both with ASD; about 80% of the cases should be idiopathic. Given the goal to quantify genetic contributions to ASD, we will also assess the Broader Autism Phenotype in family members. We will characterize co occurring but non-diagnostic behavioral problems (anxiety, motor dyspraxia, sensory sensitivities, sleep problems, and aggressive or self-injurious behavior) as well as other medical conditions. Family functioning will be assessed in the interest of understanding the effects of ASD, and responses to treatment will be monitored in the interest of future translational research. A longitudinal follow-up will allow confirmation of early diagnoses and a measure of the course of ASD. A neuroimaging study, including eye tracking and electrodermal measures, will be conducted on the subsample of twins over 8 years of age, with particular attention paid to the discordant MZ pairs.