title: Genotypes do not confer risk for delinquency but rather alter susceptibility to positive and negative environmental factors: gene-environmentinteractions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR [corrected].
abstract: 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, 1 337 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.
authors.affiliation: Centre for Clinical Research, Uppsala University, County Hospital, S-721 89 Västerås, Sweden (Drs Nilsson and Åslund); Department of Neuroscience, Uppsala University, BMC, Box 593 S-751 24 Uppsala, Sweden (Drs Comasco and Oreland); Karolinska Institutet, Stockholm Sweden, and Département de Psychiatrie, Université de Montréal, Montréal, Canada (Dr Hodgins). kent.nilsson@ltv.se.
authors.forename: Kent W
authors.initials: KW
authors.lastname: Nilsson
authors.affiliation: Centre for Clinical Research, Uppsala University, County Hospital, S-721 89 Västerås, Sweden (Drs Nilsson and Åslund); Department of Neuroscience, Uppsala University, BMC, Box 593 S-751 24 Uppsala, Sweden (Drs Comasco and Oreland); Karolinska Institutet, Stockholm Sweden, and Département de Psychiatrie, Université de Montréal, Montréal, Canada (Dr Hodgins).
authors.forename: Erika
authors.initials: E
authors.lastname: Comasco
authors.affiliation: Centre for Clinical Research, Uppsala University, County Hospital, S-721 89 Västerås, Sweden (Drs Nilsson and Åslund); Department of Neuroscience, Uppsala University, BMC, Box 593 S-751 24 Uppsala, Sweden (Drs Comasco and Oreland); Karolinska Institutet, Stockholm Sweden, and Département de Psychiatrie, Université de Montréal, Montréal, Canada (Dr Hodgins).
authors.forename: Sheilagh
authors.initials: S
authors.lastname: Hodgins
authors.affiliation: Centre for Clinical Research, Uppsala University, County Hospital, S-721 89 Västerås, Sweden (Drs Nilsson and Åslund); Department of Neuroscience, Uppsala University, BMC, Box 593 S-751 24 Uppsala, Sweden (Drs Comasco and Oreland); Karolinska Institutet, Stockholm Sweden, and Département de Psychiatrie, Université de Montréal, Montréal, Canada (Dr Hodgins).
authors.forename: Lars
authors.initials: L
authors.lastname: Oreland
authors.affiliation: Centre for Clinical Research, Uppsala University, County Hospital, S-721 89 Västerås, Sweden (Drs Nilsson and Åslund); Department of Neuroscience, Uppsala University, BMC, Box 593 S-751 24 Uppsala, Sweden (Drs Comasco and Oreland); Karolinska Institutet, Stockholm Sweden, and Département de Psychiatrie, Université de Montréal, Montréal, Canada (Dr Hodgins).
authors.forename: Cecilia
authors.initials: C
authors.lastname: Åslund
mesh_terms: D000293:Adolescent; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002650:Child Abuse, Sexual / Q000523:psychology; D004843:Epistasis, Genetic; D054541:Family Conflict / Q000523:psychology; D005260:Female; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007604:Juvenile Delinquency / Q000523:psychology*; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D010287:Parent-Child Relations; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012463:Saliva / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013548:Sweden
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C579455:BDNF protein, human; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human
keywords: brain-derived neurotrophic factor; gene-environment interaction; juvenile delinquency; monoamine oxidase; serotonin plasma membrane transport proteins