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

par Fanelli, Giuseppe;Sokolowski, Marcus;Wasserman, Danuta;Kasper, Siegfried S.F.;Zohar, Joseph;Souery, Daniel ;Montgomery, Stuart;Albani, Diego;Forloni, GianLuigi Luigi G.;Ferentinos, Panagiotis;Rujescu, Dan;Mendlewicz, Julien ;De Ronchi, Diana;Serretti, Alessandro;Fabbri, Chiara
Référence American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 189, 3-4, page (74-85)
Publication Publié, 2022-04

Article révisé par les pairs

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Résumé :

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.