Hu Wei, Liu Tian-Shu, Shen Zhen-Zhen, Tian Ge, Wang Jia-Ning, Zhao Zhen-Yu, Liu Bao-Peng, Jia Cun-Xian
Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Brain Behav Immun. 2025 Aug;128:634-642. doi: 10.1016/j.bbi.2025.05.005. Epub 2025 May 9.
Although individual lifestyle factors may be associated with suicide attempts (SA), the prospective association of composite lifestyles with SA remains unknown. Furthermore, whether this association is modulated by genetic risk remains to be elucidated. The study aimed to investigate the association of composite lifestyles and genetic risk with SA risk and to explore the underlying biological mechanisms.
435,154 individuals from the UK Biobank without a history of SA at baseline were enrolled. The SA diagnosis was based on the International Classification of Diseases coding system. Composite lifestyles were developed based on seven modifiable lifestyle factors and categorized into favorable, intermediate, and unfavorable groups. According to the polygenic risk score for SA, genetic risk was classified as low, intermediate, or high. Cox proportional hazard models and mediation analyses were conducted to examine the associations and mechanisms, respectively.
During a mean follow-up of 13.6 years, 1,515 (0.35 %) individuals experienced SA. Compared to individuals with favorable lifestyles, the HR (95 % CI) for SA among those with unfavorable lifestyles was 2.19 (1.93-2.48). The risk of SA was 68 % higher among those with high genetic risk compared with low-risk individuals (HR = 1.68, 95 % CI: 1.48-1.92). The joint test revealed that individuals with unfavorable lifestyles and high genetic risk faced the highest risk of SA (HR = 3.58, 95 % CI: 2.91-4.40), which could be explained by an additive interaction. Several biomarkers in liver function, endocrine, inflammation, and blood cell pathways collectively explained 15.84 % (95 % CI: 7.68 %-27.68 %) of the association.
Adherence to favorable lifestyles was associated with a lower risk of SA, especially among those at high genetic risk. The beneficial association might be partially explained by improvement in key mediating biomarkers.
尽管个体生活方式因素可能与自杀未遂（SA）有关，但综合生活方式与SA的前瞻性关联仍不明确。此外，这种关联是否受遗传风险的调节仍有待阐明。本研究旨在调查综合生活方式和遗传风险与SA风险的关联，并探索潜在的生物学机制。
纳入英国生物银行中435,154名基线时无SA病史的个体。SA诊断基于国际疾病分类编码系统。综合生活方式基于七个可改变的生活方式因素构建，并分为良好、中等和不良组。根据SA的多基因风险评分，将遗传风险分为低、中、高。分别进行Cox比例风险模型和中介分析以检验关联和机制。
在平均13.6年的随访期间，1515名（0.35%）个体经历了SA。与生活方式良好的个体相比，生活方式不良的个体发生SA的HR（95%CI）为2.19（1.93 - 2.48）。与低遗传风险个体相比，高遗传风险个体发生SA的风险高68%（HR = 1.68，95%CI：1.48 - 1.92）。联合检验显示，生活方式不良且遗传风险高的个体面临SA的风险最高（HR = 3.58，95%CI：2.91 - 4.40），这可以通过相加交互作用来解释。肝功能、内分泌、炎症和血细胞途径中的几种生物标志物共同解释了该关联的15.84%（95%CI：7.68% - 27.68%）。
坚持良好的生活方式与较低的SA风险相关，尤其是在高遗传风险人群中。这种有益关联可能部分由关键中介生物标志物的改善来解释。
