Prenatal exercise interventions result in subtle changes in the human breast milk metabolome and lipidome 7-14 days postpartum: exploratory analyses of the FitMum randomized controlled trial.

Schizophrenia (SCZ) encompasses a spectrum of complex psychiatric syndromes characterized by disturbances in perception, thinking, emotion, volitional behavior, and incoherence in mental activity, which typically first happens in adolescence [, ]. SCZ causes profound personal suffering and places a heavy psychosocial and economic burden on families and society []. Globally, it affects about 1% of individuals and is considered one of the leading 10 causes of disability []. For SCZ, a shorter lifespan is attributed to a higher incidence of suicide behavior. Suicide-related behaviors include suicidal ideation (SI), suicide planning (SP), suicide attempts (SA), and suicide completion (CS) []. Unlike thoughts of engagement in suicide and formulations of suicide method, SA refers to non-fatal and self-directed potentially injurious behavior in which there is at least some intent to death []. A meta-analysis including 35 studies demonstrated that the pooled lifetime rate of SA was 26.8% in SCZ []. Suicide is the most common cause of death in people with a SCZ disorder [], and young patients are most likely to attempt to kill themselves []. Suicide rates are 12 times greater among SCZ patients, and most SA occurs near the onset of disease []. Bondy et al. suggested that 43% of the susceptibility of SA could be attributed to genetic association []. Fujikane et al. summarized comorbid genetic background of psychiatric disorders in SA, and these correlations persist after accounting for mental disorders []. Although epidemiological and clinical studies consistently support a close relationship between SCZ and SA, several important issues remain unexplained. First, it is still unclear to what extent this association reflects a shared genetic architecture, rather than environmental confounding, or reverse causality. Second, while recent large-scale GWAS studies have identified susceptibility loci for SCZ and SA separately [, ], and prior studies have shown that SA is genetically correlated with multiple psychiatric phenotypes, the specific shared genetic architecture between SCZ and SA has not been systematically estimated. Third, the biological context between them remains poorly understood, including whether shared signals converge in specific tissues or genomic regions, and whether there exists a causal relationship. Therefore, in the present study, we aimed to comprehensively investigate the genetic overlap between SCZ and SA by quantifying their global and local genetic correlations, identifying shared pleiotropic loci and colocalized genetic variants, characterizing tissue-specific enrichment in both traits, and evaluating potential causal associations using bidirectional Mendelian randomization (MR). By integrating these complementary analyses, we sought to provide a more systematic understanding of the shared genetic architecture between SCZ and SA (Fig. ).