Polygenic risk scores for neuropsychiatric, inflammatory, and cardio-metabolic traits highlight possible genetic overlap with suicide attempt and treatment-emergent suicidal ideation

European College of Neuropsychopharmacology (ECNP) Network on Suicide Research and Prevention

Research output: Contribution to journalArticlepeer-review

Abstract

Suicide is the second cause of death among youths. Genetics may contribute to suicidal phenotypes and their co-occurrence in other neuropsychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for 24 neuropsychiatric, inflammatory, and cardio-metabolic traits/diseases with suicide attempt (SA) or treatment-worsening/emergent suicidal ideation (TWESI). PRSs were computed based on summary statistics of genome-wide association studies. Regression analyses were performed between PRSs and SA or TWESI in four clinical cohorts. Results were then meta-analyzed across samples, including a total of 688 patients with SA (Neff = 2,258) and 214 with TWESI (Neff = 785). Stratified genetic covariance analyses were performed to investigate functionally cross-phenotype PRS associations. After Bonferroni correction, PRS for major depressive disorder (MDD) was associated with SA (OR = 1.24; 95% CI = 1.11–1.38; p = 1.73 × 10−4). Nominal associations were shown between PRSs for coronary artery disease (CAD) (p = 4.6 × 10−3), loneliness (p =.009), or chronic pain (p =.016) and SA, PRSs for MDD or CAD and TWESI (p =.043 and p =.032, respectively). Genetic covariance between MDD and SA was shown in 86 gene sets related to drugs having antisuicidal effects. A higher genetic liability for MDD may underlie a higher SA risk. Further, but milder, possible modulatory factors are genetic risk for loneliness and CAD.

Original languageEnglish
Pages (from-to)74-85
Number of pages12
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume189
Issue number3-4
DOIs
StatePublished - 1 Apr 2022

Keywords

  • gene sets
  • major depressive disorder
  • polygenic risk scores
  • suicide
  • treatment-worsening/emergent suicidal ideation

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