Metabolic syndrome increases the risk of suicide attempt: evidence from a population-based cohort and genomic analysis

Suicide is a critical global public health issue, where traditional risk assessment tools have limited predictive value, warranting the identification of novel risk assessment factors. Metabolic syndrome (MetS) has been linked to poor cognition and brain volumes, which may lead to abnormal behaviors. The relationship between MetS and suicide risk has been less studied. This study aims to explore the association of MetS on suicide attempt leveraging data from the UK Biobank and genomic analyses. We first explored the cross-sectional and longitudinal relationships between MetS and suicide attempt, while also exploring the mediating role of cognitive performance. Second, using summary data from the largest genome-wide association studies, the genetic associations between MetS, suicide attempt, and cognitive performance were examined. Of 380,557 participants tracked over 13 years, we identified 1847 new cases of suicide attempt. The presence of MetS was found to significantly increase the risk of suicide attempt (HR = 1.250, 95% CI = 1.134-1.379). In participants lacking traditional suicide risk factors, such as being female, younger, and having higher educational attainment, MetS still presented a greater risk in predicting future suicide attempts. Additionally, MetS and suicide attempt exhibited significant genetic correlation (rg = 0.080 ± 0.026), and Mendelian randomization analysis suggested MetS had a significant negative effect on suicide attempt (β = 0.156, 95% CI = 0.077-0.235). These findings highlight a significant association between MetS and increased suicide risk. Addressing MetS may offer an avenue for improved suicide management.