Zhang Fuquan, Cao Hongbao, Baranova Ancha
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China.
Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Front Cardiovasc Med. 2021 Nov 11;8:735136. doi: 10.3389/fcvm.2021.735136. eCollection 2021.
Major depressive disorder (MDD) is phenotypically associated with cardiovascular diseases (CVD). We aim to investigate mechanisms underlying relationships between MDD and CVD in the context of shared genetic variations. Polygenic overlap analysis was used to test genetic correlation and to analyze shared genetic variations between MDD and seven cardiovascular outcomes (coronary artery disease (CAD), heart failure, atrial fibrillation, stroke, systolic blood pressure, diastolic blood pressure, and pulse pressure measurement). Mendelian randomization analysis was used to uncover causal relationships between MDD and cardiovascular traits. By cross-trait meta-analysis, we identified a set of genomic loci shared between the traits of MDD and stroke. Putative causal genes for MDD and stroke were prioritized by fine-mapping of transcriptome-wide associations. Polygenic overlap analysis pointed toward substantial genetic variation overlap between MDD and CVD. Mendelian randomization analysis indicated that genetic liability to MDD has a causal effect on CAD and stroke. Comparison of genome-wide genes shared by MDD and CVD suggests 20q12 as a pleiotropic region conferring risk for both MDD and CVD. Cross-trait meta-analyses and fine-mapping of transcriptome-wide association signals identified novel risk genes for MDD and stroke, including , and . Many genetic variations associated with MDD and CVD outcomes are shared, thus, pointing that genetic liability to MDD may also confer risk for stroke and CAD. Presented results shed light on mechanistic connections between MDD and CVD phenotypes.
重度抑郁症（MDD）在表型上与心血管疾病（CVD）相关。我们旨在研究在共享基因变异背景下MDD与CVD之间关系的潜在机制。采用多基因重叠分析来测试遗传相关性，并分析MDD与七种心血管结局（冠状动脉疾病（CAD）、心力衰竭、心房颤动、中风、收缩压、舒张压和脉压测量）之间的共享基因变异。采用孟德尔随机化分析来揭示MDD与心血管性状之间的因果关系。通过跨性状荟萃分析，我们确定了MDD和中风性状之间共享的一组基因组位点。通过全转录组关联的精细定位，对MDD和中风的推定因果基因进行了优先级排序。多基因重叠分析表明MDD和CVD之间存在大量遗传变异重叠。孟德尔随机化分析表明，MDD的遗传易感性对CAD和中风有因果影响。MDD和CVD共享的全基因组基因比较表明，20q12是一个赋予MDD和CVD风险的多效性区域。跨性状荟萃分析和全转录组关联信号的精细定位确定了MDD和中风的新风险基因，包括 ，以及 。许多与MDD和CVD结局相关的遗传变异是共享的，因此，表明MDD的遗传易感性也可能导致中风和CAD风险。呈现的结果揭示了MDD和CVD表型之间的机制联系。
