Composite lifestyle, genetic risk, blood biomarkers, and risk of suicide attempts: a prospective cohort study
Brain Behav Immun. 2025 May 9:S0889-1591(25)00183-7. doi: 10.1016/j.bbi.2025.05.005. Online ahead of print.
ABSTRACT
BACKGROUND: 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.
METHODS: 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.
FINDINGS: 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.
INTERPRETATION: 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.
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