Shared molecular mechanisms and transdiagnostic potential of neurodevelopmental disorders and immune disorders

全基因组关联研究 遗传建筑学 神经发育障碍 生物 候选基因 单核苷酸多态性 免疫系统 遗传学 自闭症 数量性状位点 遗传关联 维加维斯 计算生物学 基因 医学 基因型 精神科
作者
Zhanjie Xiu,Ling Sun,Haiyan Cao,Hui‐Qi Qu,Joseph Glessner,Zhiyong Ding,Gang Zheng,Nan Wang,Qianghua Xia,Jie Li,Håkon Håkonarson,Wei Liu,Jin Li
出处
期刊:Brain Behavior and Immunity [Elsevier]
被引量:1
标识
DOI:10.1016/j.bbi.2024.04.026
摘要

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.
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