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

Holly C. Wilcox, Janice M. Fullerton, Anne L. Glowinski, Kelly Benke, Masoud Kamali, Leslie A. Hulvershorn, Emma K. Stapp, Howard J. Edenberg, Gloria M.P. Roberts, Neera Ghaziuddin, Carrie Fisher, Christine Brucksch, Andrew Frankland, Claudio Toma, Alex D. Shaw, Elizabeth Kastelic, Leslie Miller, Melvin G. McInnis, Philip B. Mitchell, John I. Nurnberger

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1073-1080
Number of pages8
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number12
StatePublished - Dec 2017


  • attempted
  • bipolar disorder
  • polygenic risk
  • populations at risk
  • suicide
  • traumatic stress

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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