Sex-Specific Association of a Common Variant of the XG Gene With Autism Spectrum Disorders
Sex-Specific Association of a Common Variant of the XG Gene With Autism Spectrum Disorders
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DOI：
10.1002/ajmg.b.32165
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发表时间：
2013-10-01
影响因子：
2.8
通讯作者：
Santangelo, Susan L.
中科院分区：
文献类型：
--
作者：
Chang, Shun-Chiao;Pauls, David L.;Santangelo, Susan L.
自闭症谱系障碍（ASD）在男性中的发病率远高于女性。采用连锁分析和候选基因关联分析方法的研究已经确定了一些特定于所有患病者均为男性的家庭的基因变异，这表明性别可能与自闭症相关的特定基因的表达相互作用或产生其他影响。在这项研究中，我们利用自闭症遗传资源交流库的数据，采用基于家系的全基因组关联研究方法，专门评估了自闭症的性别特异性遗传效应。我们在374个欧洲血统的多成员家庭中评估了自闭症的男性特异性遗传效应，这些家庭中所有患病者均为男性（仅男性；MO），并在主要为父系起源的MO家庭中，在Xp22.33/Yp11.31染色体的拟常染色体边界上发现了一种新的全基因组显著关联（rs2535443，p = 3.8×10⁻⁸）。位于13q33.3染色体上MYO16和IRS2基因之间一个550kb基因间区域内的5个标记，在MO家庭中也显示出与自闭症的提示性关联（p = 3.3×10⁻⁵到5.3×10⁻⁷）。相比之下，在有患病女性的家庭中，这些标记似乎都与自闭症无关。我们的研究结果表明，Xp22.33/Yp11.31上的拟常染色体边界可能包含自闭症的男性特异性基因变异。（c）2013威利期刊公司
Autism spectrum disorders (ASD) are much more common in males than in females. Studies using both linkage and candidate gene association approaches have identified genetic variants specific to families in which all affected cases were male, suggesting that sex may interact with or otherwise influence the expression of specific genes in association with ASD. In this study, we specifically evaluated the sex-specific genetic effects of ASD with a family-based genome-wide association study approach using the data from the Autism Genetic Resource Exchange repository. We evaluated the male-specific genetic effects of ASD in 374 multiplex families of European ancestry in which all affected were male (male-only; MO) and identified a novel genome-wide significant association in the pseudoautosomal boundary on chromosome Xp22.33/Yp11.31 in the MO families of predominantly paternal origin (rs2535443, p=3.8x10(-8)). Five markers that reside within a 550kb intergenic region on chromosome 13q33.3, between the MYO16 and IRS2 genes, also showed suggestive association with ASD in the MO families (p=3.3x10(-5) to 5.3x10(-7)). In contrast, none of these markers appeared to be associated with ASD in the families containing any affected females. Our results suggest that the pseudoautosomal boundary on Xp22.33/Yp11.31 may harbor male-specific genetic variants for ASD. (c) 2013 Wiley Periodicals, Inc.