Guillemin Claire, Provençal Nadine, Suderman Matthew, Côté Sylvana M, Vitaro Frank, Hallett Michael, Tremblay Richard E, Szyf Moshe
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada ; Research Unit on Children's Psycho-Social Maladjustment and Ste-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada ; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada.
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada ; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada ; McGill Centre for Bioinformatics, McGill University, Montreal, Quebec, Canada.
PLoS One. 2014 Jan 24;9(1):e86822. doi: 10.1371/journal.pone.0086822. eCollection 2014.
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.
METHODOLOGY/PRINCIPAL FINDINGS: Methylation profiles were created using the method of methylated DNA immunoprecipitation (MeDIP) followed by microarray hybridization and statistical and bioinformatic analyses on T cell DNA obtained from adult women who were found to be on a chronic physical aggression trajectory (CPA) between 6 and 12 years of age compared to women who followed a normal physical aggression trajectory. We confirmed the existence of a well-defined, genome-wide signature of DNA methylation associated with chronic physical aggression in the peripheral T cells of adult females that includes many of the genes similarly associated with physical aggression in the same cell types of adult males.
This study in a small number of women presents preliminary evidence for a genome-wide variation in promoter DNA methylation that associates with CPA in women that warrant larger studies for further verification. A significant proportion of these associations were previously observed in men with CPA supporting the hypothesis that the epigenetic signature of early life aggression in females is composed of a component specific to females and another common to both males and females.
高频率的身体攻击行为是严重品行障碍的核心特征，且与广泛的社会、心理和身体健康问题相关。我们之前曾检验过这样一个假设，即外周血T细胞中不同的DNA甲基化特征与男性的慢性攻击行为轨迹有关。尽管性别差异似乎在决定攻击行为的发展、程度和频率方面起着关键作用，但此前大多数研究都集中在男性身上，因此对于女性慢性身体攻击行为知之甚少。因此，我们在此检验女性DNA甲基化中是否存在身体攻击行为的特征，如果存在，它与在男性中观察到的特征有何关联。
方法/主要发现：使用甲基化DNA免疫沉淀（MeDIP）方法创建甲基化图谱，随后进行微阵列杂交，并对从6至12岁期间被发现处于慢性身体攻击行为轨迹（CPA）的成年女性与遵循正常身体攻击行为轨迹的女性的T细胞DNA进行统计和生物信息学分析。我们证实，成年女性外周血T细胞中存在与慢性身体攻击行为相关的明确的全基因组DNA甲基化特征，其中包括许多在成年男性相同细胞类型中与身体攻击行为类似相关的基因。
这项针对少数女性的研究提供了初步证据，表明启动子DNA甲基化存在全基因组变异，这种变异与女性的CPA相关，需要进行更大规模的研究以进一步验证。这些关联中有很大一部分此前在患有CPA的男性中也观察到了，这支持了这样一种假设，即女性早期生活攻击行为的表观遗传特征由女性特有的成分和男性与女性共有的另一成分组成。
