A quantitative trait locus analysis of social responsiveness in multiplex autism families
A quantitative trait locus analysis of social responsiveness in multiplex autism families
复制标题
DOI：
10.1176/appi.ajp.164.4.656
复制
发表时间：
2007-04-01
影响因子：
17.7
通讯作者：
Geschwind, Daniel H.
中科院分区：
文献类型：
--
作者：
Duvall, Jacqueline A.;Lu, Ake;Geschwind, Daniel H.
目的：自闭症是一种复杂的遗传性疾病，具有高度异质性的表型，其表现为重复行为、语言缺陷和相互社交互动问题。作者提出了第一个全基因组扫描的社会内在表型自闭症使用社会反应量表，它提供了一个定量测量自闭症样行为，主要集中在社会关系。方法：使用社会反应量表对来自自闭症遗传资源交换的约100个具有两个或更多自闭症先证者的家庭进行非参数定量基因组扫描，以识别自闭症的位点为了确定检测到哪些额外的基因座，使用自闭症的定性诊断进行与相同自闭症群组的连锁分析。为了评估是否有可能是性别特异性遗传风险因素，队列分层的性别受影响的individual.Results：定量社会反应量表基因组扫描确定了两个位点上的染色体11和17，最高得分的染色体11（z = 3.22）。与此相反，没有连锁信号达到显着的自闭症诊断访谈修订的定性扫描。社会反应性量表扫描仅男性患者在11号和17号染色体以及4号、8号和10号染色体上的其他三个区域识别出相同的信号。结论：本研究证明了社会反应性量表定量内表型的实用性，可以使用定量行为信息来检测自闭症相关的遗传位点，这些信息可能与潜在的遗传因素更密切相关。
Objective: Autism is a complex genetic disorder with a highly heterogeneous phenotype defined by repetitive behaviors, language deficits, and problems with reciprocal social interactions. The authors present the first genome-wide scan for a social endophenotype in autism using the Social Responsiveness Scale, which provides a quantitative measure of autistic-like behavior, primarily focused on social relatedness.Method: A nonparametric quantitative genome scan was performed using the Social Responsiveness Scale in a cohort of about 100 families with two or more autistic probands from the Autism Genetic Resource Exchange to identify autism loci. To determine which additional loci were detected, linkage analysis with the same autism cohort using the qualitative diagnosis of autism was performed. To assess whether there were likely to be sex-specific genetic risk factors, the cohort was stratified by the sex of affected individuals.Results: The quantitative Social Responsiveness Scale genome scan identified two loci on chromosomes 11 and 17, with the highest score on chromosome 11 (z = 3.22). In contrast, no linkage signals reached significance in the Autism Diagnostic Interview-Revised qualitative scan. The Social Responsiveness Scale scan with only male affecteds identified the same signals on chromosomes 11 and 17, as well as three other regions on chromosomes 4, 8, and 10.Conclusions: This study demonstrates the utility of the Social Responsiveness Scale quantitative endophenotype to detect autism-related genetic loci using quantitative behavioral information that may more closely relate to underlying genetic factors.