A phenome-wide association and Mendelian randomization study for suicide attempt within UK Biobank.

Uncertainties persist in the neurological and behavioral risk factors for suicide attempt (SA) due to a lack of data covering multiple phenotypes. Here, the polygenic risk scores (PRSs) for SA samples within the UK Biobank (N = 40,369) were estimated using non-overlapping Psychiatric Genomics Consortium datasets as a reference. A total of 70 PRS-associated phenotypes encompassing discovered and never-reported phenotypes were identified, thereby facilitating applications in SA identification (area under the curve of 84%). Different with the existing observational studies, the causal effects between brain and SA were explored. Mendelian randomization supported a potential causal effect of right hippocampal gray matter volume on SA, whereas SA had a reverse causal effect on the VI cerebellum. After controlling for the effects of psychiatric disorders, the right hippocampus still had an independent causal effect on SA. These findings provide multi-perspective evidence for early understanding and identification of SA and shed new lights for causal inference between brain and SA.