F43. EFFECTS OF CANDIDATE GENES AND POLYGENIC RISK ON THE DEVELOPMENT OF DEPRESSION IN A PEER VICTIMIZED POPULATION

Background Peer victimization (i.e., bullying) is a common form of childhood adversity, where over 30% of children across the globe have reported being victimized. Children who have experienced peer victimization have an increased susceptibility to various psychiatric disorders including depression. However, environmental influences can have varying degrees of effect between individuals, and therefore further research is required to understand 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 have been conducted in the past for depression, but with inconsistent findings. Recent genetic studies have identified the effect of polygenic risk on the disorder, where polygenic risk scores (PRS) obtained from genome-wide association studies (GWAS) can be used to predict the risk of developing depression. 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 22 (n=349). A computer-based questionnaire was used to obtain participants peer victimization experience from age 10 to 18, and Indirect Aggression Scale Target Version was used for participants from age 19 to 22. Depression symptoms were measured using the Behavioral Assessment System for Children-2, and an adult version of the questionnaire was used from age 19 to 22. Monoamine oxidase A gene (MAOA) and dopamine transporter gene (DAT1/SLC6A3) have been selected to conduct candidate gene analysis to determine the variable number tandem repeats (VNTRs) of each participant using polymerase chain reaction and gel electrophoresis. Quality control analysis have been conducted prior to GWAS to increase precision and accuracy of the dataset. We will then conduct GWAS using PLINK v.1.96 to identify the genetic variants associated with depression as a quantitative trait. Using the data obtained from GWAS, PRS for depression will be calculated for each participant using PRSice-2. Multiple linear regression analysis will be performed utilizing the genetic findings from the candidate gene analysis and estimated polygenic risk score. History of childhood peer victimization will be included as an interaction term to investigate G x E interactions associated between environmental and genetic factors on the development of depressive symptoms. Results The VNTRs for DAT1 gene were found to be within the range of 3-13 repeats (203 - 603 base pairs). The VNTRs for MAOA gene have been found to be within the range of 2-6 repeats (291 - 411 base pairs). DNA samples of 337 participants were successfully genotyped on the Infinium Global Screening Array-24 v1.0 with 730,059 markers. Upon completion of the quality control analysis, 490,434 variants and 301 participants passed the quality control filters. Discussion Through the findings, both candidate genetic variants and polygenic risk scores may potentially explain individual differences in the development of depression following adverse environmental exposures, such as peer victimization. The significance of the research is that minimal studies to date have specifically examined the interaction between polygenic risk and peer victimization experience on depression longitudinally through adolescence.