F68. INCREASED POLYGENIC RISK FOR MAJOR PSYCHIATRIC DISORDERS IN A SPANISH SAMPLE OF SUICIDE DEATH CASES

• Published in: European neuropsychopharmacology Vol. 87; pp. 242 - 243
• Main Authors: Papiol, Sergi, Vila, Judit Tella, Giner, Lucas, Guija, Julio Antonio, Schulze, Thomas, Falkai, Peter, Cervilla, Jorge, Gutierrez, Blanca
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2024
• ISSN: 0924-977X
• DOI: 10.1016/j.euroneuro.2024.08.479

Suicide currently represents a major public health crisis, showing a concerning 36 % increase over the past two decades [WHO, 2023]. Suicide is a leading cause of death worldwide, accounting for close to 800,000 deaths per year according to recent estimates. Suicide ranks among the leading causes of death, particularly among young individuals (ages between 10 and 34 years) in the United States [Centers for Disease Control and Prevention]. Severe psychiatric conditions such as major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have been identified as relevant risk factors for suicidal behavior. Likewise, evidence suggest that suicidal behavior has its own genetic component, independent from psychiatric conditions [Li et al., 2022]. To gain insights into the genetic architecture and etiology of this complex phenotype, in this study we used polygenic risk scores (PRS) for different psychiatric traits to estimate their role in the risk of suicide in a large Spanish sample of suicide death cases. A final sample of 2,299 subjects (728 suicide death cases, 1571 controls) of Spanish origin was analyzed in this study. After genotyping with Global Screening Array chipset, quality control was performed using standard procedures described elsewhere [Boudriot et al., 2024]. Genotype imputation was carried out in the Michigan Imputation Server, using the HRC r1.1 2016 reference panel. Subsequently, PRS-CS tool was used to infer posterior SNP effect sizes under continuous shrinkage priors and estimate the global shrinkage parameter (φ) using a fully Bayesian approach (auto model) [Ge et al., 2019]. PRS were calculated for different phenotypes, including SCZ, BD, MDD, and suicide death (SD), and suicide attempt (SA). Subsequently the association of polygenic load with status (SD cases versus healthy controls) was analyzed using binary logistic regression models while correcting for age, sex, and population ancestry principal components. SCZ-PRS and BD-PRS were associated with suicide death in our sample, explaining, respectively, 4.1 % (p value < 0.05) and 4.0 % (p value  < 0.05) of the variance in the observed scale. In both cases the genetic load for SCZ or BD is higher in suicide death cases. No significant association was found when using MDD-PRS, SD-PRS, or SA-PRS (p value > 0.05). Our analysis shows that the genetic load for SCZ and BP plays a role in the risk of suicide, replicating previous findings [Mitjans et al., 2022]. However, the effects of MDD-PRS could not be replicated [Doherty et al., 2020]. These data align with previous results regarding the high prevalence of mental disorders among the subjects dead by suicide. These results also align with the increasing evidence of an extensive genetic overlap between psychiatric diagnoses and their associated traits, with suicide representing the most severe outcome of these disorders.