The polygenic nature and the contribution of common genetic variation to autism spectrum disorder (ASD) allude to a high degree of pleiotropy between ASD and other psychiatric and behavioral traits. In a pleiotropic system, a single genetic variant contributes small effects to several phenotypes or disorders. While analyzed broadly, there is a paucity of research studies investigating the shared genetic information between specific neurodevelopmental domains and ASD. We performed a phenome-wide association study of ASD polygenetic risk score (PRS) against 491 neurodevelopmental subdomains ascertained in 4,309 probands from the Philadelphia Neurodevelopmental Cohort (PNC) who lack an ASD diagnosis. Our main analysis calculated ASD PRS in 4,309 PNC probands using the per-SNP effects reported in a recent genome-wide association studies of ASD in a case-control design. In a high-resolution manner, our main analysis regressed ASD PRS against 491 neurodevelopmental phenotypes with age, sex, and ten principal components of ancestry as covariates. Follow-up analyses included in the regression model PRS derived from brain-related traits genetically correlated with ASD. Our main finding demonstrated that 11-17-year old probands with the highest ASD genetic risk were able to identify angry faces (R² = 1.06%, p = 1.38 × 10⁻⁷, p_{Bonferroni-corrected} = 1.9 × 10⁻³). This ability replicated in older probands (>18 years; R² = 0.55%, p = 0.036) and persisted after covarying with other psychiatric disorders, brain imaging traits, and educational attainment (R² = 0.2%, p = 0.019). We also detected several suggestive associations between ASD PRS and emotionality and connectedness with others. These data (i) indicate how genetic liability to ASD may influence neurodevelopment in the general population, (ii) reinforce epidemiological findings of heightened ability of ASD cases to predict certain social psychological events based on increased systemizing skills (iii) recapitulate theories of imbalance between empathizing and systemizing in ASD etiology.

多基因性质和常见遗传变异对自闭症谱系障碍 (ASD) 的贡献暗示了 ASD 与其他精神和行为特征之间的高度多效性。在多效性系统中，单个遗传变异对几种表型或疾病的影响很小。虽然进行了广泛的分析，但很少有研究调查特定神经发育域和 ASD 之间共享的遗传信息。我们针对来自费城神经发育队列 (PNC) 的 4,309 名缺乏 ASD 诊断的先证者中确定的 491 个神经发育子域进行了 ASD 多基因风险评分 (PRS) 的全表型关联研究。我们的主要分析计算了 4 中的 ASD PRS，309 名 PNC 先证者使用 per-SNP 效应在最近的 ASD 全基因组关联研究中报告的病例对照设计。以高分辨率的方式，我们的主要分析将 ASD PRS 针对 491 种神经发育表型进行回归，将年龄、性别和祖先的 10 个主要成分作为协变量。包含在回归模型 PRS 中的后续分析源自与 ASD 遗传相关的大脑相关特征。我们的主要发现表明，具有最高 ASD 遗传风险的 11-17 岁先证者能够识别愤怒的面孔（R 包含在回归模型 PRS 中的后续分析源自与 ASD 遗传相关的大脑相关特征。我们的主要发现表明，具有最高 ASD 遗传风险的 11-17 岁先证者能够识别愤怒的面孔（R 包含在回归模型 PRS 中的后续分析源自与 ASD 遗传相关的大脑相关特征。我们的主要发现表明，具有最高 ASD 遗传风险的 11-17 岁先证者能够识别愤怒的面孔（R² = 1.06%，p = 1.38 × 10 ^-7，p _{Bonferroni 校正}= 1.9 × 10 ^-3）。这种能力在老年先证者（> 18 岁；R ² = 0.55%，p = 0.036）中复制，并在与其他精神疾病、脑成像特征和教育程度共变后持续存在（R ²= 0.2%，p = 0.019）。我们还发现了 ASD PRS 与情绪和与他人的联系之间的一些暗示性关联。这些数据 (i) 表明 ASD 的遗传倾向如何影响一般人群的神经发育，(ii) 加强了 ASD 病例基于提高的系统化技能预测某些社会心理事件的能力增强的流行病学发现 (iii) 概括了之间不平衡的理论在 ASD 病因学中的同理心和系统化。