Yrigollen Carolyn M, Han Summer S, Kochetkova Anna, Babitz Tammy, Chang Joseph T, Volkmar Fred R, Leckman James F, Grigorenko Elena L
Department of Statistics, Department of Epidemiology and PublicHealth, Yale University, NewHaven, CT 06519-1124, USA.
Biol Psychiatry. 2008 May 15;63(10):911-6. doi: 10.1016/j.biopsych.2007.11.015. Epub 2008 Jan 22.
Autism spectrum disorders (ASD) are neurodevelopmental disorders of complex etiology, with a recognized substantial contribution of heterogeneous genetic factors; one of the core features of ASD is a lack of affiliative behaviors.
On the basis of the existing literature, in this study we examined the hypothesis of allelic associations between genetic variants in six genes involved in control of maternal and affiliative behaviors (OXT, OXTR, PRL, PRLR, DbetaH, and FOSB). One hundred and seventy-seven probands with ASD from 151 families (n = 527) were assessed with a set of related instruments capturing multiple facets of ASD. Multivariate and univariate phenotypes were constructed from these assessments and subjected to genetic linkage and association analyses with PBAT and FBAT software.
The resulting pattern of findings, in general, confirmed the hypotheses of the significance of the genes involved in the development of affiliative behaviors in the manifestation of ASD (p values ranging from .000005 to .05); statistically speaking, the strongest results were obtained for allelic associations with the PRL, PRLR, and OXTR genes.
These preliminary data provide additional support for the hypothesis that the allelic variants of genes necessary for the development of species-typical affiliative behaviors are associated with ASD. Independent replication of these findings is needed and studies of other genes associated with affiliative behaviors are indicated.
自闭症谱系障碍（ASD）是病因复杂的神经发育障碍，已知多种遗传因素起着重要作用；ASD的核心特征之一是缺乏亲和行为。
基于现有文献，在本研究中我们检验了参与母体和亲和行为控制的六个基因（OXT、OXTR、PRL、PRLR、DbetaH和FOSB）的基因变异之间等位基因关联的假设。来自151个家庭（n = 527）的177名ASD先证者使用一组相关工具进行评估，这些工具涵盖了ASD的多个方面。从这些评估中构建多变量和单变量表型，并使用PBAT和FBAT软件进行遗传连锁和关联分析。
总体而言，所得结果模式证实了参与亲和行为发展的基因在ASD表现中的重要性这一假设（p值范围为0.000005至0.05）；从统计学上讲，与PRL、PRLR和OXTR基因的等位基因关联获得了最强的结果。
这些初步数据为物种典型亲和行为发展所需基因的等位基因变异与ASD相关这一假设提供了额外支持。需要对这些发现进行独立重复验证，并开展与亲和行为相关的其他基因的研究。
