Song Qifeng, Zhang Cheng, Wang Wei, Wang Cihan, Yi Chenlong
Department of Cardiovascular Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225000, China.
Nanjing Vocational Health College, Nanjing, Jiangsu 210000, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111172. doi: 10.1016/j.pnpbp.2024.111172. Epub 2024 Oct 17.
The genetic links between heart disease and psychiatric disorders are complex and not well understood. This study uses genome-wide association studies (GWAS) and advanced multilevel analyses to explore these connections.
We analyzed GWAS data from seven psychiatric disorders and five types of heart disease. Genetic correlations and overlaps were examined using linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), and Genetic analysis incorporating Pleiotropy and Annotation (GPA). Pleiotropic single-nucleotide variations (SNVs) were identified with pleiotropic analysis under the composite null hypothesis (PLACO) and annotated via Functional mapping and annotation of genetic associations (FUMA). Potential pleiotropic genes were identified using Multi-marker Analysis of GenoMic Annotation (MAGMA) and Summary data-based Mendelian Randomization (SMR).
Among 35 trait pairs, 32 showed significant genetic correlations or overlaps. PLACO identified 15,077 SNVs, with 287 recognized as pleiotropic loci and 20 colocalization sites. MAGMA and SMR revealed 75 potential pleiotropic genes involved in diverse pathways, including cancer, neurodevelopment, and cellular organization. Mouse Genome Informatics (MGI) queries provided evidence linking multiple genes to heart or psychiatric disorders.
This analysis reveals loci and genes with pleiotropic effects between heart disease and psychiatric disorders, highlighting shared biological pathways. These findings illuminate the genetic mechanisms underlying the brain-heart axis and suggest shared biological foundations for these conditions, offering potential targets for future prevention and treatment strategies.
心脏病与精神疾病之间的遗传联系复杂且尚未完全明晰。本研究采用全基因组关联研究（GWAS）和先进的多水平分析来探究这些关联。
我们分析了来自七种精神疾病和五种心脏病类型的GWAS数据。使用连锁不平衡评分回归（LDSC）、高清似然性（HDL）以及纳入多效性和注释的遗传分析（GPA）来检查遗传相关性和重叠情况。在复合零假设（PLACO）下通过多效性分析鉴定多效性单核苷酸变异（SNV），并通过遗传关联的功能映射和注释（FUMA）进行注释。使用基因组注释的多标记分析（MAGMA）和基于汇总数据的孟德尔随机化（SMR）来鉴定潜在的多效性基因。
在35个性状对中，32个显示出显著的遗传相关性或重叠。PLACO鉴定出15,077个SNV，其中287个被识别为多效性位点，20个共定位位点。MAGMA和SMR揭示了75个潜在的多效性基因，涉及多种途径，包括癌症、神经发育和细胞组织。小鼠基因组信息学（MGI）查询提供了将多个基因与心脏病或精神疾病联系起来的证据。
该分析揭示了心脏病和精神疾病之间具有多效性作用的位点和基因，突出了共享的生物学途径。这些发现阐明了脑 - 心轴背后的遗传机制，并表明这些病症具有共同的生物学基础，为未来的预防和治疗策略提供了潜在靶点。
