Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts

Abstract

Objective Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). Method Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. Results After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). Conclusion BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability.

Diverse phenotypic measurements of wellbeing: Heritability, temporal stability and the variance explained by polygenic scores

“…Prior to imputation using the Michigan Imputation Server (v1.0.3), 17 genotypes of 1333 participants underwent pre‐imputation QC following the ENIGMA2 protocols (Phase 3, version 5), and were combined after pre‐imputation QC with 1472 other Caucasian cohort samples, also genotyped on PsychArray at Mt Sinai, 18 to maximize the sample and improve imputation accuracy. Details of pre‐imputation quality control, identity‐by‐descent and principal component analysis (PCA) and imputation details are provided in Supplementary Online Material.…”

Studying individual risk factors for self-harm in the UK Biobank: A polygenic scoring and Mendelian randomisation study

“…A PS for schizophrenia predicted SSH among offspring of suicide attempters [25] and in a population sample [27], but not in another clinical sample [28]. A PS for bipolar disorder predicted SSH in 1 clinical sample [29] but did not predict SSH nor NSSH among offspring of suicide attempters [25] or relatives of PLOS MEDICINE bipolar disorder patients [30]. A recently published study showed that PSs for cannabis use and MDD predicted self-harm in the UK Biobank sample [31].…”

Childhood maltreatment and polygenic risk in bipolar disorders

“…17 Finally, the interaction between BD polygenic risk score and childhood maltreatment was significantly associated with suicide attempts in a sample of relatives of patients with BD and healthy controls. 18 To date, no investigations of the interactions between BD-PRS and childhood maltreatment on the clinical expression of BD has been published and further explorations are thus warranted.…”