M62: TWO SIDES OF THE SAME COIN: SHARED POLYGENIC RISK OF PERSONALITY TRAITS AND SUICIDE ATTEMPT IMPLICATES COMMON PATHOMECHANISMS IN IMPAIRED EXECUTIVE FUNCTIONING AND EXTERNALIZING DISORDERS

Abstract

Background Suicide undoubtedly is the most devastating complications of psychiatric disorders. The link between suicide and mental health problems is strong, particularly for mood disorders and personality disorders. Growing evidence suggest large extent of shared etiology and psychopathology between psychiatric and personality disorders, even indicating the theory of a unified, general psychopathological dimension behind all mental disorder. However, little is known about the common genetic risk factors of personality traits and suicidal behavior. The aim of our study was to assess the extent of the shared genetic etiology between suicidal behavior and the NEO Big Five personality traits (NEO-FFI) by conducting a Polygenic Risk Score prediction (PRS) analysis. Methods Target sample of the PRS analysis included subject with BPD from the GAIN Whole Genome Association Study of Bipolar Disorder (accession: phs000017.v3.p1, total n=999, suicidal n=358, control n=616, missing n=25) Suicidal attempt was assessed with the Diagnostic Interview for Genetic Studies versions 2,3 and 4. To increase the genomic overlap between the training and target datasets, GAIN BPD samples were imputed by using SHAPEIT and IMPUTE2 with 1000 Genomes Project s Phase I v3 reference genome. SNP-based associations were tested with PLINK, whereas PRS analyses were carried out by using PRSice. PRS scores for each NEO-FFI personality traits were computed from the publicly available summary result files of the first phase of the Genetics of Personality Consortium GWAS meta-analysis (GPC1, 10 cohorts, n=17,375 subjects). All PRS models were adjusted for sex, age and potential population stratification. Results Nominally significant PRS prediction of suicidal attempt in the target sample were only shown for Conscientiousness at pt Discussion Polygenic profile score analysis suggest shared genetic etiology between suicidal attempt and certain personality traits. Since Conscientiousness kinks both externalizing and internalizing behaviors, and low Conscientiousness scores and high Extraversion scores correlate with impaired executive functioning, our findings confirm the involvement of executive functions in the pathomechanism of suicide and support the theory of a general psychopathologic dimension. However, due to the relatively small size of the target sample, and the modest strength of PRS predictions, our findings should be interpreted cautiously.