童年逆境与心血管疾病风险：揭示血浆蛋白质组通路及遗传易感性的调节作用
Childhood Adversity and Cardiovascular Disease Risk: Unraveling Plasma Proteomic Pathways and Moderating Role of Genetic Predisposition.
摘要(中文译文)
儿童期逆境（CA）与心血管疾病（CVD）相关。蛋白质组学分析可能有助于阐明其潜在机制。本研究旨在探讨儿童期逆境与遗传风险如何共同影响心血管疾病以及蛋白质组学生物标志物的潜在作用。研究共纳入来自英国生物银行的14 508名基线无心血管疾病且具有可用蛋白质组学数据的参与者。儿童期逆境采用儿童期创伤筛查问卷进行评估。蛋白质组学特征通过最小绝对收缩和选择算子回归得出。采用Cox比例风险模型检验儿童期逆境与心血管疾病的关联，并进行中介分析以评估蛋白质组学生物标志物对这些关联的解释程度。在中位随访13.5年期间，共识别出2 286例新发心血管疾病事件。儿童期逆境评分每增加1分与全因及病因特异性心血管疾病相关，全因心血管疾病、冠心病、心律失常/传导障碍和心力衰竭的风险比（HR）分别为1.049（95% CI，1.031-1.068）、1.039（95% CI，1.009-1.070）、1.041（95% CI，1.015-1.067）和1.066（95% CI，1.012-1.122）。未观察到儿童期逆境与遗传风险之间存在显著交互作用。同时具有高儿童期逆境和高遗传风险的参与者全因心血管疾病风险最高（HR，1.847 [95% CI，1.380-2.472]）。若干蛋白质（前肾上腺髓质素、集聚蛋白、AHNAK、CD302、CD83和Yes相关蛋白1）解释了儿童期逆境与全因及病因特异性心血管疾病关联的1.58%至9.98%。蛋白质组学特征在统计学上中介了这些关联的3.68%至10.80%。儿童期逆境与遗传易感性共同导致心血管疾病风险增加。蛋白质组学生物标志物部分中介了儿童期逆境与心血管疾病的关联，为连接早期生活逆境与心血管疾病的生物学通路提供了见解。
Abstract
Childhood adversity (CA) is associated with cardiovascular disease (CVD). Proteomic profiling may help elucidate underlying mechanisms. This study aimed to explore how CA and genetic risk jointly impact CVD and the potential role of proteomic biomarkers. A total of 14 508 participants without baseline CVD and with available proteomics data from the UK Biobank were included. CA was assessed using the Childhood Trauma Screener questionnaire. Proteomic signatures were derived using least absolute shrinkage and selection operator regression. Cox proportional hazard models were used to examine the associations of CA with CVD, and mediation analyses were conducted to assess the extent to which proteomic biomarkers explained these associations. Over a median follow-up of 13.5 years, 2286 incident CVD events were identified. The per-score increase in CA score was associated with all-cause and cause-specific CVD, with hazard ratios (HRs) for all-cause CVD, coronary heart disease, arrhythmia/conduction disorder, and heart failure being 1.049 (95% CI, 1.031-1.068), 1.039 (95% CI, 1.009-1.070), 1.041 (95% CI, 1.015-1.067), and 1.066 (95% CI, 1.012-1.122), respectively. No significant interaction between CA and genetic risk was observed. Participants with both high CA and high genetic risk had the highest all-cause CVD risk (HR, 1.847 [95% CI, 1.380-2.472]). Several proteins (pro-adrenomedullin, agrin, AHNAK, CD302, CD83, and yes-associated protein 1) explained 1.58% to 9.98% of the associations between CA and all-cause and cause-specific CVD. Proteomic signatures statistically mediated 3.68% to 10.80% of these associations. CA and genetic susceptibility jointly contributed to increased CVD risk. Proteomic biomarkers partially mediate the CA-CVD associations, providing insight into biological pathways linking early-life adversity and CVD.
如何引用
AMA
Jiang-Yan Wang, Chang Liu, Xiao-Yu Jia, Jia-Ning Wang, Cun-Xian Jia, Bao-Peng Liu. Childhood Adversity and Cardiovascular Disease Risk: Unraveling Plasma Proteomic Pathways and Moderating Role of Genetic Predisposition.. Journal of the American Heart Association. 2026; doi:10.1161/JAHA.125.048564.
APA
Jiang-Yan Wang, Chang Liu, Xiao-Yu Jia, Jia-Ning Wang, Cun-Xian Jia, Bao-Peng Liu (2026). Childhood Adversity and Cardiovascular Disease Risk: Unraveling Plasma Proteomic Pathways and Moderating Role of Genetic Predisposition.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.048564
GB/T 7714
Jiang-Yan Wang, Chang Liu, Xiao-Yu Jia, Jia-Ning Wang, Cun-Xian Jia, Bao-Peng Liu. Childhood Adversity and Cardiovascular Disease Risk: Unraveling Plasma Proteomic Pathways and Moderating Role of Genetic Predisposition.[J]. Journal of the American Heart Association, 2026 doi:10.1161/JAHA.125.048564.
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