Zhang Jianfei, Qiu Hao, Zhao Qiyu, Liao Chongjian, Guoli Yuxuan, Luo Qi, Zhao Guoshu, Zhang Nannan, Wang Shaoying, Zhang Zhihui, Lei Minghuan, Liu Feng, Peng Yanmin
College of Computer and Control Engineering, Qiqihar University, Qiqihar, Heilongjiang, China.
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.
Schizophrenia (Heidelb). 2024 Mar 5;10(1):31. doi: 10.1038/s41537-024-00453-5.
Schizophrenia (SCZ), a highly heritable mental disorder, is characterized by cognitive impairment, yet the extent of the shared genetic basis between schizophrenia and cognitive performance (CP) remains poorly understood. Therefore, we aimed to explore the polygenic overlap between SCZ and CP. Specifically, the bivariate causal mixture model (MiXeR) was employed to estimate the extent of genetic overlap between SCZ (n = 130,644) and CP (n = 257,841), and conjunctional false discovery rate (conjFDR) approach was used to identify shared genetic loci. Subsequently, functional annotation and enrichment analysis were carried out on the identified genomic loci. The MiXeR analyses revealed that 9.6 K genetic variants are associated with SCZ and 10.9 K genetic variants for CP, of which 9.5 K variants are shared between these two traits (Dice coefficient = 92.8%). By employing conjFDR, 236 loci were identified jointly associated with SCZ and CP, of which 139 were novel for the two traits. Within these shared loci, 60 exhibited consistent effect directions, while 176 had opposite effect directions. Functional annotation analysis indicated that the shared genetic loci were mainly located in intronic and intergenic regions, and were found to be involved in relevant biological processes such as nervous system development, multicellular organism development, and generation of neurons. Together, our findings provide insights into the shared genetic architecture between SCZ and CP, suggesting common pathways and mechanisms contributing to both traits.
精神分裂症（SCZ）是一种具有高度遗传性的精神障碍，其特征为认知障碍，然而精神分裂症与认知表现（CP）之间共享遗传基础的程度仍知之甚少。因此，我们旨在探究SCZ与CP之间的多基因重叠情况。具体而言，采用双变量因果混合模型（MiXeR）来估计SCZ（n = 130,644）和CP（n = 257,841）之间的遗传重叠程度，并使用联合错误发现率（conjFDR）方法来识别共享的基因座。随后，对所识别的基因组位点进行功能注释和富集分析。MiXeR分析显示，9.6K个基因变异与SCZ相关，10.9K个基因变异与CP相关，其中9.5K个变异在这两个性状之间共享（迪西系数 = 92.8%）。通过使用conjFDR，共识别出236个与SCZ和CP共同相关的位点，其中139个是这两个性状的新位点。在这些共享位点中，60个表现出一致的效应方向，而176个具有相反的效应方向。功能注释分析表明，共享的基因座主要位于内含子和基因间区域，并发现其参与了神经系统发育、多细胞生物体发育和神经元生成等相关生物学过程。总之，我们的研究结果为SCZ和CP之间共享的遗传结构提供了见解，表明存在导致这两个性状的共同途径和机制。
