Liu Hao, Sun Yang, Zhang Xinxin, Li Shiyang, Hu Dong, Xiao Lei, Chen Yanghui, He Lin, Wang Dao Wen
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China.
Front Psychiatry. 2020 Apr 17;11:256. doi: 10.3389/fpsyt.2020.00256. eCollection 2020.
Genome-wide association studies (GWAS) have identified abundant risk loci associated with schizophrenia (SCZ), cardiometabolic disease (CMD) including body mass index, coronary artery diseases, type 2 diabetes, low- and high-density lipoprotein, total cholesterol, and triglycerides. Although recent studies have suggested that genetic risk shared between these disorders, the pleiotropic genes and biological pathways shared between them are still vague. Here we integrated comprehensive multi-dimensional data from GWAS, expression quantitative trait loci (eQTL), and gene set database to systematically identify potential pleiotropic genes and biological pathways shared between SCZ and CMD. By integrating the results from different approaches including FUMA, Sherlock, SMR, UTMOST, FOCUS, and DEPICT, we revealed 21 pleiotropic genes that are likely to be shared between SCZ and CMD. These genes include , , , , , , , , , , , , , , , , , , , and . In addition, we also performed the gene-set enrichment analysis using the software of GSA-SNP2 and MAGMA with GWAS summary statistics and identified three biological pathways (MAPK-TRK signaling, growth hormone signaling, and regulation of insulin secretion signaling) shared between them. Our study provides insights into the pleiotropic genes and biological pathways underlying mechanisms for the comorbidity of SCZ and CMD. However, further genetic and functional studies are required to validate the role of these potential pleiotropic genes and pathways in the etiology of the comorbidity of SCZ and CMD, which should provide potential targets for future diagnostics and therapeutics.
全基因组关联研究（GWAS）已经确定了大量与精神分裂症（SCZ）、心血管代谢疾病（CMD）相关的风险位点，心血管代谢疾病包括体重指数、冠状动脉疾病、2型糖尿病、低密度和高密度脂蛋白、总胆固醇以及甘油三酯。尽管最近的研究表明这些疾病之间存在遗传风险共享，但它们之间共享的多效性基因和生物学途径仍然不明确。在这里，我们整合了来自GWAS、表达定量性状位点（eQTL）和基因集数据库的全面多维数据，以系统地识别SCZ和CMD之间共享的潜在多效性基因和生物学途径。通过整合来自不同方法（包括FUMA、Sherlock、SMR、UTMOST、FOCUS和DEPICT）的结果，我们揭示了21个可能在SCZ和CMD之间共享的多效性基因。这些基因包括 ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， 。此外，我们还使用GSA-SNP2和MAGMA软件对GWAS汇总统计数据进行了基因集富集分析，并确定了它们之间共享的三种生物学途径（MAPK-TRK信号传导、生长激素信号传导和胰岛素分泌信号调节）。我们的研究为SCZ和CMD共病的潜在多效性基因和生物学途径提供了见解。然而，需要进一步的遗传和功能研究来验证这些潜在的多效性基因和途径在SCZ和CMD共病病因中的作用，这应该为未来的诊断和治疗提供潜在靶点。
