The brain-heart axis: Integrative analysis of the shared genetic etiology between neuropsychiatric disorders and cardiovascular disease

作者全名：Chen, Feifan; Dong, Xinyu; Yu, Zhiwei; Zhang, Yihan; Shi, Yuan

作者地址：[Chen, Feifan; Zhang, Yihan; Shi, Yuan] Chongqing Med Univ, Childrens Hosp,Natl Clin Res Ctr Child Hlth & Diso, Dept Neonatol,Chongqing Key Lab Child Rare Dis Inf, Minist Educ Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China; [Dong, Xinyu] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Neurosurg,Childrens Hosp,Chongqing Key Lab Pe, Minist Educ Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China; [Yu, Zhiwei] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Neurol,Childrens Hosp,Chongqing Key Lab Child, Minist Educ Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China; [Shi, Yuan] Chongqing Med Univ, Childrens Hosp, Chongqing 400014, Peoples R China

通信作者：Shi, Y (通讯作者)，Chongqing Med Univ, Childrens Hosp, Chongqing 400014, Peoples R China.

来源：JOURNAL OF AFFECTIVE DISORDERS

ESI学科分类：PSYCHIATRY/PSYCHOLOGY

WOS号：WOS:001225643600001

JCR分区：Q1

影响因子：4.9

年份：2024

卷号：355

期号：　

开始页：147

结束页：156

文献类型：Article

关键词：The brain-heart Axis; Neuropsychiatric disorders; Cardiovascular disease; LDSC; Mendelian randomization; FUMA

摘要：Background: Multiple observational studies have reported substantial comorbidity between neuropsychiatric disorders and cardiovascular disease (CVD), but the underlying mechanisms remain largely unknown. Methods: Using GWAS summary datasets of 8 neuropsychiatric disorders and 6 cardiovascular diseases, an integrative analysis incorporating linkage-disequilibrium-score-regression (LDSC), Mendelian randomization (MR), functional mapping and annotation (FUMA), and functional enrichment analysis, was conducted to investigate shared genetic etiology of the brain-heart axis from the whole genome level, single-nucleotide polymorphism (SNP) level, gene level, and biological pathway level. Results: In LDSC analysis, 18 pairwise traits between neuropsychiatric disorders and CVD were identified with significant genetic overlaps, revealing extensive genome-wide genetic correlations. In bidirectional MR analysis, 19 pairwise traits were identified with significant causal relationships. Genetic liabilities to neuropsychiatric disorders, particularly attention-deficit hyperactivity disorder and major depressive disorder, conferred extensive significant causal effects on the risk of CVD, while hypertension seemed to be a risk factor for multiple neuropsychiatric disorders, with no significant heterogeneity or pleiotropy. In FUMA analysis, 13 shared independent significant SNPs and 887 overlapping protein-coding genes were detected between neuropsychiatric disorders and CVD. With GO and KEEG functional enrichment analysis, biological pathways of the brain-heart axis were highly concentrated in neurotransmitter synaptic transmission, lipid metabolism, aldosterone synthesis and secretion, glutathione metabolism, and MAPK signaling pathway. Conclusion: Extensive genetic correlations and genetic overlaps between neuropsychiatric disorders and CVD were identified in this study, which might provide some new insights into the brain-heart axis and the therapeutic targets in clinical practice.

基金机构：National Key Research and Devel-opment Program of China [2022YFC2704803]

基金资助正文：<B>Funding</B> This work was supported by the National Key Research and Devel-opment Program of China (2022YFC2704803) .