Autism spectrum disorders (ASDs) are highly heritable and result in abnormal repetitive behaviors and impairment in communication and cognitive skills. Previous studies have focused on the genetic correlation between ASDs and other neuropsychiatric disorders, but an in-depth understanding of the correlation to other disorders is required. We conducted an extensive meta-analysis of common variants identified in ASDs by genome-wide association studies (GWAS) and compared it to the consensus genes and single nucleotide polymorphisms (SNPs) of Schizophrenia (SCZ). We found approximately 75% of the GWAS genes that are associated with ASD are also associated with SCZ. We further investigated the cellular phenotypes of neurons derived from induced pluripotent stem cell (iPSC) models in ASD and SCZ. Our findings revealed that ASD and SCZ neurons initially follow divergent developmental trajectories compared to control neurons. However, despite these early diametrical differences, both ASD and SCZ neurons ultimately display similar deficits in synaptic activity as they mature. This significant genetic overlap between ASD and SCZ, coupled with the convergence towards similar synaptic deficits, highlights the intricate interplay of genetic and developmental factors in shaping the shared underlying mechanisms of these complex neurodevelopmental and neuropsychiatric disorders.

自闭症谱系障碍 (ASD) 具有高度遗传性，会导致异常重复行为以及沟通和认知技能受损。先前的研究主要集中在自闭症谱系障碍与其他神经精神疾病之间的遗传相关性，但需要深入了解与其他疾病的相关性。我们对全基因组关联研究 (GWAS) 中发现的 ASD 常见变异进行了广泛的荟萃分析，并将其与精神分裂症 (SCZ) 的共有基因和单核苷酸多态性 (SNP) 进行了比较。我们发现大约 75% 与 ASD 相关的 GWAS 基因也与 SCZ 相关。我们进一步研究了 ASD 和 SCZ 中诱导多能干细胞 (iPSC) 模型衍生的神经元的细胞表型。我们的研究结果表明，与对照神经元相比，ASD 和 SCZ 神经元最初遵循不同的发育轨迹。然而，尽管存在这些早期的直径差异，ASD 和 SCZ 神经元最终在成熟时都表现出类似的突触活动缺陷。 ASD 和 SCZ 之间的这种显着的遗传重叠，加上类似突触缺陷的趋同，凸显了遗传和发育因素在塑造这些复杂的神经发育和神经精神疾病的共同潜在机制中复杂的相互作用。