Examining and interpreting the female protective effect against autistic behavior
Examining and interpreting the female protective effect against autistic behavior
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DOI：
10.1073/pnas.1211070110
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发表时间：
2013-03-26
影响因子：
11.1
通讯作者：
Ronald, Angelica
中科院分区：
文献类型：
--
作者：
Robinson, Elise B.;Lichtenstein, Paul;Ronald, Angelica
男性在自闭症行为障碍中的优势一直被解释为女性性别的假设保护作用，但很少有研究对这一假设进行实证检验。如果女性受到保护，她们应该需要更大的病因负荷才能表现出与男性相同程度的损害。这项分析的目的是检查与男性相比，女性更大的家庭病因负荷是否与定量自闭症障碍有关。受试者包括来自双胞胎早期发育研究（TEDS）的3，842对双卵双胞胎和来自瑞典儿童和青少年双胞胎研究（CATSS）的6，040对双卵双胞胎。在这两个样本中，我们比较了女性和男性先证者之间的兄弟姐妹自闭症特征，这些先证者被确定为在人群自闭症特征分布中排名前90位和第95位的儿童。在TEDS和CATSS中，高于第90百分位数的女性先证者的兄弟姐妹比高于第90百分位数的男性先证者的兄弟姐妹有更多的自闭症障碍。在TEDS和CATSS中，第90百分位数以上的女性先证者的兄弟姐妹也有更大的分类复发风险。结果在第95百分位以上的先证者中相似。这一发现，在两个全国代表性的样本中重复，表明女性性别保护女孩免受自闭症障碍，女孩可能需要更大的家族病因负荷来表现表型。它为女性对自闭症行为的保护作用的假设提供了实证支持，并可用于告知和解释未来在自闭症谱系障碍中的基因发现工作。
Male preponderance in autistic behavioral impairment has been explained in terms of a hypothetical protective effect of female sex, yet little research has tested this hypothesis empirically. If females are protected, they should require greater etiologic load to manifest the same degree of impairment as males. The objective of this analysis was to examine whether greater familial etiologic load was associated with quantitative autistic impairments in females compared with males. Subjects included 3,842 dizygotic twin pairs from the Twins Early Development Study (TEDS) and 6,040 dizygotic twin pairs from the Child and Adolescent Twin Study of Sweden (CATSS). In both samples, we compared sibling autistic traits between female and male probands, who were identified as children scoring in the top 90th and 95th percentiles of the population autistic trait distributions. In both TEDS and CATSS, siblings of female probands above the 90th percentile had significantly more autistic impairments than the siblings of male probands above the 90th percentile. The siblings of female probands above the 90th percentile also had greater categorical recurrence risk in both TEDS and CATSS. Results were similar in probands above the 95th percentile. This finding, replicated across two nationally-representative samples, suggests that female sex protects girls from autistic impairments and that girls may require greater familial etiologic load to manifest the phenotype. It provides empirical support for the hypothesis of a female protective effect against autistic behavior and can be used to inform and interpret future gene finding efforts in autism spectrum disorders.