Project description:Animal and human studies suggest that inflammation is associated with behavioral disorders including aggression. We have recently shown that physical aggression of boys during childhood is strongly associated with reduced plasma levels of cytokines IL-1a, IL-4, IL-6, IL-8 and IL-10, later in early adulthood (Provencal et al., unpublished data). This study tests the hypothesis that there is an association between differential DNA methylation regions in cytokine genes in T cells and monocytes DNA in adult subjects and a trajectory of physical aggression from childhood to adolescence. We compared the methylation profiles of the entire genomic loci encompassing the IL-1a, IL-6, IL-4, IL10 and IL8 and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6 genes in adult males on a chronic physical aggression trajectory (CPA) and males with the same background who followed a normal physical aggression trajectory (control group). We used the method of methylated DNA immunoprecipitation (MeDIP) with comprehensive cytokine gene loci and TF loci microarray hybridization, statistical analysis and false discovery rate correction.
Project description:Animal and human studies suggest that inflammation is associated with behavioral disorders including aggression. We have recently shown that physical aggression of boys during childhood is strongly associated with reduced plasma levels of cytokines IL-1a, IL-4, IL-6, IL-8 and IL-10, later in early adulthood (Provencal et al., unpublished data). This study tests the hypothesis that there is an association between differential DNA methylation regions in cytokine genes in T cells and monocytes DNA in adult subjects and a trajectory of physical aggression from childhood to adolescence. We compared the methylation profiles of the entire genomic loci encompassing the IL-1a, IL-6, IL-4, IL10 and IL8 and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6 genes in adult males on a chronic physical aggression trajectory (CPA) and males with the same background who followed a normal physical aggression trajectory (control group). We used the method of methylated DNA immunoprecipitation (MeDIP) with comprehensive cytokine gene loci and TF loci microarray hybridization, statistical analysis and false discovery rate correction. We recruited two groups of Caucasian males who were born in families with a low socioeconomic status and were living at the time of the present study within 200km from our laboratory. The first group, composed of 8 subjects, had a history of chronic physical aggression from age 6 to 15 years (chronic physical aggression group, CPA). The second group, composed of 12 subjects, was recruited from the same longitudinal studies but included only those who did not have a history of chronic physical aggression from age 6 to 15 (Control group, CG). Using custom-designed microarrays with 44K probes tiling cytokines IL-1a, IL-6, IL-4, IL10 and IL8 and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6, we obtained DNA methylation profiles by meDIP-chip. Each profile was generated in triplicate.
Project description:Chronic physical aggression (CPA) is characterized by frequent use of physical aggression from early childhood to adolescence. Observed in approximately 5% of males, it is associated with early childhood adverse environments. DNA methylation, a covalent modification of DNA, regulates genome function and has been associated with early childhood adverse environments. We analyzed T cell DNA genome-wide promoter methylation profiles from two groups of adult males assessed annually for frequency of physical aggression between 6 and 15 years of age: a group with CPA and a control group. Whole genome methylation analysis was performed using MeDIP followed by hybridization to microarrays. We mapped the promoter regions of 20 000 genes and 400 microRNAs. The subjects were recruited from participants in two longitudinal studies of child development9,47. We recruited two groups of Caucasian males who were born in families with a low socioeconomic status and were living at the time of the present study within 200km from our laboratory. The first group had a history of high physical aggression from age 6 to 15 years (chronic physical aggression group, CPA). The second group was recruited from the same longitudinal studies but included only those who did not have a history of high physical aggression from age 6 to 15 (Control group). A total of 65 eligible subjects agreed to participate (8 CPA and 57 controls). Using custom-designed microarrays with 244K probes tiling the promoter regions of 20000 genes and 400 microRNAs, we obtained DNA methylation profiles by meDIP-chip. Each profile was generated in triplicate.
Project description:High frequency of physical aggression is the central feature of severe conduct disorder and is associated with a wide range of social, mental and physical health problems. We have previously tested the hypothesis that differential DNA methylation signatures in peripheral T cells are associated with a chronic aggression trajectory in males. Despite the fact that sex differences appear to play a pivotal role in determining the development, magnitude and frequency of aggression, most of previous studies focused on males, so little is known about female chronic physical aggression. We therefore tested here whether or not there is a signature of physical aggression in female DNA methylation and, if there is, how it relates to the signature observed in males. Genome-wide promoter methylation profiles of T cell DNA from adult females on a Chronic Physical Aggression (CPA, n=5) trajectory during childhood and adolescence were compared to those on normative physical aggression trajectories (NPA, n=14). Two technical replicates were generated for each individual.
Project description:Chronic physical aggression (CPA) is characterized by frequent use of physical aggression from early childhood to adolescence. Observed in approximately 5% of males, it is associated with early childhood adverse environments. DNA methylation, a covalent modification of DNA, regulates genome function and has been associated with early childhood adverse environments. We analyzed T cell DNA genome-wide promoter methylation profiles from two groups of adult males assessed annually for frequency of physical aggression between 6 and 15 years of age: a group with CPA and a control group. Whole genome methylation analysis was performed using MeDIP followed by hybridization to microarrays. We mapped the promoter regions of 20 000 genes and 400 microRNAs.
Project description:High frequency of physical aggression is the central feature of severe conduct disorder and is associated with a wide range of social, mental and physical health problems. We have previously tested the hypothesis that differential DNA methylation signatures in peripheral T cells are associated with a chronic aggression trajectory in males. Despite the fact that sex differences appear to play a pivotal role in determining the development, magnitude and frequency of aggression, most of previous studies focused on males, so little is known about female chronic physical aggression. We therefore tested here whether or not there is a signature of physical aggression in female DNA methylation and, if there is, how it relates to the signature observed in males. Genome-wide promoter methylation profiles of T cell DNA from adult males and females on a Chronic Physical Aggression (CPA) trajectory during childhood and adolescence were compared to adults on a normative physical aggression trajectories (NPA). Each sample was bisulphite converted gDNA pooled in equimolar amounts. Three different pools of genomic DNA were made per group: male CPA (2 or 3 different subjects per pool), male NPA (4 different subjects per pool), female CPA (2 different subjects per pool) and female NPA (4 or 5 different subjects per pool) . The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles of the 2 groups in both sex.
Project description:High frequency of physical aggression is the central feature of severe conduct disorder and is associated with a wide range of social, mental and physical health problems. We have previously tested the hypothesis that differential DNA methylation signatures in peripheral T cells are associated with a chronic aggression trajectory in males. Despite the fact that sex differences appear to play a pivotal role in determining the development, magnitude and frequency of aggression, most of previous studies focused on males, so little is known about female chronic physical aggression. We therefore tested here whether or not there is a signature of physical aggression in female DNA methylation and, if there is, how it relates to the signature observed in males.
Project description:High frequency of physical aggression is the central feature of severe conduct disorder and is associated with a wide range of social, mental and physical health problems. We have previously tested the hypothesis that differential DNA methylation signatures in peripheral T cells are associated with a chronic aggression trajectory in males. Despite the fact that sex differences appear to play a pivotal role in determining the development, magnitude and frequency of aggression, most of previous studies focused on males, so little is known about female chronic physical aggression. We therefore tested here whether or not there is a signature of physical aggression in female DNA methylation and, if there is, how it relates to the signature observed in males.