PDF(Pubmed)
Abstract：
Autism is four times more prevalent in males than females. To study whether this reflects a difference in genetic predisposition attributed to autosomal rare variants, we evaluated the sex differences in effect size of damaging protein-truncating and missense variants on autism predisposition in 47,061 autistic individuals, then compared effect sizes between individuals with and without cognitive impairment or motor delay. Although these variants mediated differential likelihood of autism with versus without motor or cognitive impairment, their effect sizes on the liability scale did not differ significantly by sex exome-wide or in genes sex-differentially expressed in the cortex. Although de novo mutations were enriched in genes with male-biased expression in the fetal cortex, the liability they conferred did not differ significantly from other genes with similar loss-of-function intolerance and sex-averaged cortical expression. In summary, autosomal rare coding variants confer similar liability for autism in females and males.
摘要：
自闭症在男性中的患病率是女性的四倍。为了研究这是否反映了归因于常染色体罕见变异的遗传易感性的差异，我们评估了47,061名自闭症个体中破坏性蛋白质截断和错义变体对自闭症易感性的影响大小的性别差异，然后比较有和没有认知障碍或运动延迟的个体之间的效应大小。尽管这些变异介导了有运动或认知障碍的自闭症与无自闭症的不同可能性，它们在责任量表上的效应大小在不同性别外显子组范围内或在皮质中性别差异表达的基因中没有显著差异.尽管新生突变在胎儿皮质中具有男性偏向表达的基因中富集，它们赋予的责任与具有类似功能丧失不耐受和性别平均皮质表达的其他基因没有显著差异.总之,常染色体罕见编码变异赋予女性和男性自闭症相似的责任。
