Background. Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child–parent relationship, and teenage delinquency.
Methods. In 2006, as part of the Survey of Adolescent Life in Västmanland, Sweden, 1337 high-school students, aged 17–18 years, anonymously completed questionnaires and provided saliva samples for DNA analyses.
Results. Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met×5-HTTLPR×MAOA-uVNTR×family conflicts, and for BDNF Val66Met×5-HTTLPR×MAOA-uVNTR×sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL (girls) and L (boys) vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met×5-HTTLPR S×MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child–parent relationship.
Conclusions. Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency
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