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Monoamine oxidase A genotype and methylation moderate the association of maltreatment and aggressive behaviour
David Checknita1, Megha Bendre2, Tomas J Ekström3
1Department of Neuroscience, Uppsala University, Uppsala Biomedical Center, Husargatan 3, 751 24, Uppsala, Sweden; Department of Clinical Neuroscience, Centre for Psychiatry Research (CPF), Norra Stationsgatan 69, 7th floor, 113 64 Stockholm, Sweden; Centre for Clinical Research, Uppsala University, Västmanland County Council, Västmanlands Sjukhus Västerås, 721 89, Västerås, Sweden.
Background:
The association between childhood maltreatment and subsequent aggressive behaviour is modified by monoamine oxidase A (MAOA) functional polymorphism (MAOA-uVNTR) genotype, MAOA-Long (MAOA-L) in females, MAOA-Short (MAOA-S) in males. Childhood maltreatment is associated with differential DNA methylation in several genes. Consistent with recent proposals, we hypothesized that the association of the interaction of MAOA genotype and maltreatment with aggressive behaviour is further moderated by methylation of a region of interest (ROI) spanning the first exon and partial first intron of MAOA.
Method:
The sample included 117 women and 77 men who completed interviews and questionnaires to report maltreatment and aggressive behaviour towards others and provided saliva samples for DNA extraction. The MAOA-uVNTR polymorphism was genotyped, and methylation of the MAOA ROI was assessed.
Results:
Following adjustment for substance misuse, psychoactive medication use, and in males tobacco use, the highest levels of aggressive behaviour were found among maltreated male carriers of MAOA-S with high levels of exonic methylation.
Conclusion:
Methylation levels within the MAOA ROI further contributed to the interaction of MAOA risk genotypes and maltreatment on aggressive behaviours among men.
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