Effects of Candidate Genes and Polygenic Risk on the Development of Depression in Youth Experiencing Peer Victimization

Abstract

Background: Peer victimization is a common form of childhood adversity, where children who have experienced victimization have an increased susceptibility to various psychiatric disorders including depression. However, environmental influences have varying degrees of effect between individuals, and therefore our study focused on how genetic predisposition in conjunction with environmental factors interacts to confer risk for depression. Gene by environment (G x E) interaction studies with a focus on candidate genes and polygenic risk scores (PRS-depression) have been conducted in the past for depression, but with inconsistent findings. Testing both candidate genes and PRS, and their interaction with environmental factors, may be a promising approach for understanding the complex aetiology of depression. Methods: Longitudinal data from the McMaster Teen Study have been obtained, where students initially assessed from age 10 (Grade 5) were followed to age 26 (n=875). A computer-based self-reported questionnaire was used to obtain participants’ peer victimization experience and depressive symptoms from age 10 to 26, along with their genotype data. Dopamine transporter gene (DAT1/SLC6A3), monoamine oxidase A gene (MAOA), and the serotonin transporter gene (SLC6A4) were selected for candidate gene analysis. Depression-PRS was calculated using the genome-wide metaanalysis of depression by Howard et al. (2019). Results: Peer victimization was significantly associated with depressive symptoms in adolescence (p < 0.05). Candidate gene polymorphisms and depression-PRS were not significantly associated with depressive symptoms (p > 0.05). Furthermore, there were no significant candidate gene by peer victimization and PRS-depression by peer victimization interactions associated with depressive symptoms. Conclusion: Through our study, findings suggest that exposure to peer victimization experience was independently associated with an increased risk of depressive symptoms in adolescence. Both candidate genetic variants and polygenic risk scores did not have a significant main effect on depression risk. Lastly, neither candidate gene risk nor polygenic risk of study participants were significantly associated with depression following peer victimization experiences. Future studies will greatly enhance our knowledge on how genetic risk plays a potential role in explaining individual differences in the development of depression following adverse environmental exposures, including peer victimization. Keywords: Peer victimization, depression, candidate gene, polygenic risk score, gene by environment interaction, adolescence