Sung Yun Ju, Dawson Geraldine, Munson Jeffrey, Estes Annette, Schellenberg Gerard D, Wijsman Ellen M
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195-7720, USA.
Am J Hum Genet. 2005 Jan;76(1):68-81. doi: 10.1086/426951. Epub 2004 Nov 16.
Autism is a severe developmental disorder of unknown etiology but with evidence for genetic influences. Here, we provide evidence for a genetic basis of several quantitative traits that are related to autism. These traits, from the Broader Phenotype Autism Symptom Scale (BPASS), were measured in nuclear families, each ascertained through two probands affected by autism spectrum disorder. The BPASS traits capture the continuum of severity of impairments and may be more informative for genetic studies than are the discrete diagnoses of autism that have been used by others. Using a sample of 201 nuclear families consisting of a total of 694 individuals, we implemented multivariate polygenic models with ascertainment adjustment to estimate heritabilities and genetic and environmental correlations between these traits. Our ascertainment adjustment uses conditioning on the phenotypes of probands, requires no modeling of the ascertainment process, and is applicable to multiplex ascertainment and multivariate traits. This appears to be the first such implementation for multivariate quantitative traits. The marked difference between heritability estimates of the trait for language onset with and without an ascertainment adjustment (0.08 and 0.22, respectively) shows that conclusions are sensitive to whether or not an ascertainment adjustment is used. Among the five BPASS traits that were analyzed, the traits for social motivation and range of interest/flexibility show the highest heritability (0.19 and 0.16, respectively) and also have the highest genetic correlation (0.92). This finding suggests a shared genetic basis of these two traits and that they may be most promising for future gene mapping and for extending pedigrees by phenotyping additional relatives.
自闭症是一种病因不明的严重发育障碍，但有证据表明其受遗传因素影响。在此，我们为与自闭症相关的几个数量性状的遗传基础提供了证据。这些性状来自广义自闭症症状量表（BPASS），在核心家庭中进行测量，每个家庭通过两名受自闭症谱系障碍影响的先证者确定。BPASS性状捕捉了损伤严重程度的连续体，对于遗传研究可能比其他人使用的自闭症离散诊断更具信息性。我们使用了一个由201个核心家庭组成的样本，共计694人，实施了带有确定调整的多变量多基因模型，以估计这些性状之间的遗传力以及遗传和环境相关性。我们的确定调整基于先证者的表型进行条件设定，无需对确定过程进行建模，适用于多重确定和多变量性状。这似乎是首次对多变量数量性状进行此类实施。有和没有确定调整时语言起始性状的遗传力估计值之间的显著差异（分别为0.08和0.22）表明，结论对是否使用确定调整很敏感。在分析的五个BPASS性状中，社会动机和兴趣范围/灵活性性状显示出最高的遗传力（分别为0.19和0.16），并且遗传相关性也最高（0.92）。这一发现表明这两个性状有共同的遗传基础，并且它们可能对未来的基因定位以及通过对更多亲属进行表型分析来扩展家系最为有前景。
