A Twin Study of Autism Spectrum Disorder

描述（由申请人提供）：本申请寻求五年的支持，以进行第一次基于人群的自闭症谱系障碍（ASD）双胞胎研究，使用当前诊断标准确定病例。关于自闭症遗传影响程度的推断，关键取决于同卵（MZ）与异卵（DZ）双胞胎的差异一致性。双生子研究的结果影响了各种连锁方法的可行性。不断变化的诊断实践导致基础率和双胞胎先证者识别的差异，因此需要新的研究。此外，还需要对双胞胎进行基于人群的研究，以调查双胞胎在ASD病例中的比例过高的说法。 建立在广泛的数据，建立该项目的可行性，我们将收集几乎所有的双胞胎年龄在2-16岁的威斯康星州，首先通过筛选和病例发现，然后进行全面的诊断和行为评估的状态。我们计划最终的样本为>120对双胞胎，其中一个或两个患有ASD;大约80%的病例应该是特发性的。考虑到量化遗传对ASD的贡献的目标，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但非诊断性行为问题（焦虑，运动障碍，感觉敏感性，睡眠问题和攻击性或自我伤害行为）以及其他医疗条件。为了了解ASD的影响，将对家庭功能进行评估，并为了未来的转化研究，将监测对治疗的反应。纵向随访将允许确认早期诊断和测量ASD的病程。将对8岁以上双胞胎的子样本进行神经成像研究，包括眼动追踪和皮肤电测量，特别注意不一致的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.