Polygenic risk scores for neuropsychiatric, inflammatory, and cardio-metabolic traits highlight possible genetic overlap with suicide attempt and treatment-emergent suicidal ideation.
Am J Med Genet B Neuropsychiatr Genet
; 189(3-4): 74-85, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35191176
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.
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Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
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Transtorno Depressivo Maior
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Adolescent
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article