Distinguishing clinical and genetic risk factors for suicidal ideation and behavior in a diverse hospital population

Abstract

Suicidal ideation (SI) and behavior (SB) are major public health concerns, but risk factors for their development and progression are poorly understood. We used ICD codes and a natural language processing algorithm to identify individuals in a hospital biobank with SI-only, SB, and controls without either. We compared the profiles of SB and SI-only patients to controls, and each other, using phenome-wide association studies (PheWAS) and polygenic risk scores (PRS). PheWAS identified many risk factors for SB and SI-only, plus specific psychiatric disorders which may be involved in progression from SI-only to SB. PRS for suicide attempt were only associated with SB, and even after accounting for psychiatric disorder PRS. SI PRS were only associated with SI-only, although not after accounting for psychiatric disorder PRS. These findings advance understanding of distinct genetic and clinical risk factors for SB and SI-only, which will aid in early detection and intervention efforts.

Fig. 1. Comparison of sociodemographic and behavioral characteristics between individuals with and without different suicide outcomes.

Suicidal behavior (SB) cases and suicidal ideation (SI)-only cases were compared to determine their differences from controls and from each other. Values represent either means (for age) or percentages (for all others). Bonferroni-corrected significance threshold: p < 2.38 × 10⁻³. * indicates a statistically significant difference between two groups.

Fig. 2. PheWAS of suicide outcomes in BioMe.

PheWAS results comparing (A) SB cases and controls in the upper plot and (B) SI-only cases and controls in the lower plot. Color filled boxes indicate phecodes that were also significantly associated in the comparison between SB cases and SI-only cases. Some significant associations are not labeled for legibility, but full results can be found in Supplementary Tables 6–8. The dashed lines on the y-axes indicate the Bonferroni-corrected significance thresholds: SB vs. controls p = 5.59 × 10⁻⁵ and SI-only vs. controls p = 5.63 × 10⁻⁵.