Is common genetic risk for psychiatric disorders associated with traumatic experiences in youth?

Alison K. Merikangas PhD, MPH (1,2,3), Laura M. Schultz PhD (2,3), Zoe Rapisardo-Drigot (1,4), PNC Collaborators (3,5), Laura Almasy PhD (1,2,3) 1. Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 2. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 3. Lifespan Brain Institute of the Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, PA 4. Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 5. Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

Background Although standard methods that test gene-environment interaction assume that genetics and environment are not correlated, most work on this topic has not systematically tested this assumption. Here we examine whether there are genetic influences on trauma exposure that could mediate the well-established association between trauma and psychopathology in a community sample of youth. Method The sample includes 5168 European-ancestry (EA) and 3170 African-ancestry (AA) youth (ages 8 to 21 years; 51.7% female) from the Philadelphia Neurodevelopmental Cohort. Trauma exposure was assessed with a standardized psychopathology screener administered to the youth. Polygenic scores (PGS) for several traits were calculated and their association with the number of traumas was tested. Due to the lack of comparable genome-wide association study data, different conditions were tested in EA and AA youth. Height PGS was calculated as a control in both samples, along with major depressive disorder, schizophrenia, post-traumatic stress disorder, and suicide attempt, whereas PGS for intelligence quotient (IQ), attention deficit hyperactivity disorder (ADHD), and bipolar disorder, were calculated in the EA subset only. Results In the EA subset, 1963 youth (38.1%) had experienced trauma (1208 (23.4%) experienced 1, 482 (9.3%) experienced 2, and 273 (5.3%) experienced 3 or more). Statistically significant associations were found for PGS for ADHD (p=2.8x10-6), IQ (p=1.40x10-4), and suicide attempts (p=2.40x10-3) and traumatic events. In the AA subset 1726 youth (54.6%) had experienced trauma (736 (23.2%) had experienced 1, 522 (16.5%) had experienced 2, and 468 (14.8%) had experienced 3 or more). No associations were found between PGS and trauma in the AA subset. Discussion These findings provide preliminary evidence that genetics and environment may be correlated and that exposure to traumatic childhood events may in part be attributable to common genetic factors. Our analyses were limited by the lack of comparable GWAS in the two ancestry groups. Future work on these associations will consider sex, socio-economic status, and other potential environmental correlates of traumatic events.