Polygenic risk scores for neuropsychiatric, inflammatory, and cardio-metabolic traits highlight possible genetic overlap with suicide attempt and treatment-emergent suicidal ideation.
Giuseppe FanelliMarcus SokolowskiDanuta Wassermannull nullSiegfried KasperJoseph ZoharDaniel SoueryStuart MontgomeryDiego AlbaniGianluigi ForloniPanagiotis FerentinosDan RujescuJulien MendlewiczDiana De RonchiAlessandro SerrettiChiara FabbriPublished in: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (2022)
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 (N eff = 2,258) and 214 with TWESI (N eff = 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.
Keyphrases
- major depressive disorder
- coronary artery disease
- genome wide
- bipolar disorder
- chronic pain
- copy number
- dna methylation
- type diabetes
- healthcare
- oxidative stress
- cardiovascular disease
- heart failure
- social support
- percutaneous coronary intervention
- magnetic resonance
- cardiovascular events
- depressive symptoms
- transcription factor
- combination therapy
- acute coronary syndrome
- smoking cessation
- drug induced
- replacement therapy