Parental support moderates the interaction of COMT and BDNF genotypes with early life adversity on problem gambling severity index scores among young adults.

The development of gambling-related harm and gambling disorder involves several genetic and environmental factors. However, how these factors interact to influence the development and whether such interactions confer to diathesis-stress or differential susceptibility models remains largely unexplored. To address this gap, data from the Survey of Adolescent Life in Västmanland (SALVe cohort) were utilized, Participants provided a saliva sample for genotyping, completed early life adversity (ELA) and Parents as Social Construct (PASCQ) surveys at age 17, and the Problem Gambling Severity Index (PGSI) at age 23. A total of 391 participants (54% females) with complete data were included for analysis. Negative binomial models were utilized to examine the interaction between candidate genes (COMT, BDNF, and DRD2), ELA, and parental support in PGSI scores. Interactions between COMT and BDNF, ELA, and parental support were found but not for DRD2, (β = -0.01 and -0.009, 95% CI [-0.02, -0.006 and -0.01, -0.005], p = 2.2 × 10-5 and 1.2 × 10-5 respectively). The interactions remained significant after accounting for sex interactions, p = 0.005. Notably, evidence for a differential susceptibility framework was found in gambling-related harm scores. Participants with the major allele for both COMT and BDNF displayed plasticity by exhibiting higher PGSI scores when exposed to weak parental support but lower PGSI scores in strong parental support despite higher ELA scores. Positive parental support acted as a protective factor against the genetic sensitivity of gambling-related harm. Studies pursuing the interplay between genetic and environmental factors would benefit from including positive environments that may mitigate the risk associated with adverse environments.