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创伤后应激障碍与心血管成像、风险及诊断的共享遗传结构。

Shared genetic architecture of posttraumatic stress disorder with cardiovascular imaging, risk, and diagnoses.

作者信息

Shen Jie, Valentim Wander, Friligkou Eleni, Overstreet Cassie, Choi Karmel W, Koller Dora, O'Donnell Christopher J, Stein Murray B, Gelernter Joel, Lv Haitao, Sun Ling, Falcone Guido J, Polimanti Renato, Pathak Gita A

机构信息

Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China.

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.

出版信息

Nat Commun. 2025 Jul 1;16(1):5631. doi: 10.1038/s41467-025-60487-w.

Abstract

Patients with post-traumatic stress disorder face increased cardiovascular risk. This study examines shared genetic regions between post-traumatic stress disorder and 246 cardiovascular conditions across electronic health records, 82 cardiac imaging, and health behaviors defined by Life's Essential 8. Post-traumatic stress disorder is genetically correlated with cardiovascular diagnoses in 33 regions, imaging traits in 4 regions, and health behaviors in 44 regions. Potentially shared causal variants between post-traumatic stress disorder and 17 cardiovascular conditions were observed in 11 regions. Subsequent observational analysis in AllofUS cohort showed post-traumatic stress disorder is associated with 13 diagnoses even after accounting for socioeconomic factors and depression. Genetically regulated proteome expression in brain and blood tissues identified 33 blood and 122 brain genes shared between the two conditions, revealing neuronal, immune, metabolic, and calcium-related mechanisms, with several genes as targets for existing drugs. These findings exhibit shared risk loci and genes are involved in tissue-specific mechanisms.

摘要

创伤后应激障碍患者面临更高的心血管疾病风险。本研究通过电子健康记录、82项心脏成像以及由“生命八大要素”定义的健康行为,研究了创伤后应激障碍与246种心血管疾病之间的共同遗传区域。创伤后应激障碍在33个区域与心血管疾病诊断存在遗传相关性,在4个区域与成像特征存在遗传相关性,在44个区域与健康行为存在遗传相关性。在11个区域观察到创伤后应激障碍与17种心血管疾病之间潜在的共同因果变异。在AllofUS队列中的后续观察分析表明,即使在考虑了社会经济因素和抑郁症之后,创伤后应激障碍仍与13种疾病诊断相关。对大脑和血液组织中基因调控的蛋白质组表达分析发现,两种疾病共有33个血液基因和122个大脑基因,揭示了神经元、免疫、代谢和钙相关机制,其中几个基因是现有药物的靶点。这些发现表明存在共同的风险基因座,且基因参与了组织特异性机制。

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