Megha Bendre1,2, Erika Comasco1, Dave Checknita1,2,3, Jari Tiihonen4, Sheilagh Hodgins5, Kent W Nilsson2. 1. Department of Neuroscienc, Uppsala University, Uppsala, Sweden. 2. Centre for Clinical Research, Uppsala University, County Hospital, Västerås, Sweden. 3. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 4. Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden. 5. Institut Universitaire en Santé Mentale de Montréal, Université de Montréal, Montréal, Canada.
Abstract
BACKGROUND: Epigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the monoamine oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on 53 young adult males and aimed to determine whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment, and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment. METHODS: MAOA-uVNTR genotypes with ≤ 3 and > 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman's method, respectively. RESULTS: Carriers of the S allele, who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score in contrast to L-allele carriers. Carriers of the S allele, who reported higher AUDIT-C score and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L-allele carriers. CONCLUSIONS: Intronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males.
BACKGROUND: Epigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the monoamine oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on 53 young adult males and aimed to determine whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment, and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment. METHODS:MAOA-uVNTR genotypes with ≤ 3 and > 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman's method, respectively. RESULTS: Carriers of the S allele, who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score in contrast to L-allele carriers. Carriers of the S allele, who reported higher AUDIT-C score and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L-allele carriers. CONCLUSIONS: Intronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males.
Authors: Yohanna de Oliveira; Raquel Patrícia Ataíde Lima; Rafaella Cristhine Pordeus Luna; Mussara Gomes Cavalcanti Alves Monteiro; Cássia Surama Oliveira da Silva; Rayner Anderson Ferreira do Nascimento; Keylha Querino de Farias Lima; Ana Hermínia Andrade E Silva; Flávia Emília Leite de Lima Ferreira; Rodrigo Pinheiro de Toledo Vianna; Ronei Marcos de Moraes; Naila Francis Paulo de Oliveira; Aléssio Tony Cavalcanti de Almeida; Alexandre Sérgio Silva; Alcides da Silva Diniz; Maria José de Carvalho Costa; Maria da Conceição Rodrigues Gonçalves Journal: J Transl Med Date: 2018-06-05 Impact factor: 5.531