Abstract：
The co-occurrence and familial clustering of neurodevelopmental disorders and immune disorders suggest shared genetic risk factors. Based on genome-wide association summary statistics from five neurodevelopmental disorders and four immune disorders, we conducted genome-wide, local genetic correlation and polygenic overlap analysis. We further performed a cross-trait GWAS meta-analysis. Pleotropic loci shared between the two categories of diseases were mapped to candidate genes using multiple algorithms and approaches. Significant genetic correlations were observed between neurodevelopmental disorders and immune disorders, including both positive and negative correlations. Neurodevelopmental disorders exhibited higher polygenicity compared to immune disorders. Around 50%-90% of genetic variants of the immune disorders were shared with neurodevelopmental disorders. The cross-trait meta-analysis revealed 154 genome-wide significant loci, including 8 novel pleiotropic loci. Significant associations were observed for 30 loci with both types of diseases. Pathway analysis on the candidate genes at these loci revealed common pathways shared by the two types of diseases, including neural signaling, inflammatory response, and PI3K-Akt signaling pathway. In addition, 26 of the 30 lead SNPs were associated with blood cell traits. Neurodevelopmental disorders exhibit complex polygenic architecture, with a subset of individuals being at a heightened genetic risk for both neurodevelopmental and immune disorders. The identification of pleiotropic loci has important implications for exploring opportunities for drug repurposing, enabling more accurate patient stratification, and advancing genomics-informed precision in the medical field of neurodevelopmental disorders.
摘要：
神经发育障碍和免疫障碍的共同发生和家族聚集性提示共同的遗传风险因素。基于来自五种神经发育障碍和四种免疫障碍的全基因组关联汇总统计，我们进行了全基因组，局部遗传相关和多基因重叠分析。我们进一步进行了跨性状GWAS荟萃分析。使用多种算法和方法将两类疾病之间共享的趋性基因座映射到候选基因。在神经发育障碍和免疫障碍之间观察到显着的遗传相关性，包括正相关和负相关。与免疫疾病相比，神经发育障碍表现出更高的多源性。大约50％-90％的免疫疾病的遗传变异与神经发育障碍共有。交叉性状荟萃分析揭示了154个全基因组显著基因座，包括8个新的多效性位点。观察到30个基因座与两种疾病的显着关联。对这些基因座的候选基因的途径分析揭示了这两种疾病共有的共同途径，包括神经信号，炎症。回应,和PI3K-Akt信号通路。此外,30个铅SNP中的26个与血细胞性状相关。神经发育障碍表现出复杂的多基因结构，一部分个体患有神经发育和免疫疾病的遗传风险增加。多效性基因座的鉴定对于探索药物再利用的机会具有重要意义。实现更准确的患者分层，并在神经发育障碍的医学领域推进基因组学信息的精确性。
