Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Biol Psychiatry. 2014 Jan 1;75(1):9-17. doi: 10.1016/j.biopsych.2013.05.004. Epub 2013 Jun 18.
In a seminal study of gene-environment interaction, childhood maltreatment predicted antisocial behavior more strongly in male subjects carrying an MAOA promoter variant of lesser, compared with higher, transcriptional efficiency. Many further investigations have been reported, including studies of other early environmental exposures and female subjects. Here, we report a meta-analysis of studies testing the interaction of MAOA genotype and childhood adversities on antisocial outcomes in predominantly nonclinical samples.
Included were 27 peer-reviewed, English-language studies published through August, 2012, that contained indicators of maltreatment or other family (e.g., parenting, sociodemographic) hardships; MAOA genotype; indices of aggressive and antisocial behavior; and statistical test of genotype-environment interaction. Studies of forensic and exclusively clinical samples, clinical cohorts lacking proportionally matched control subjects, or outcomes nonspecific for antisocial behavior were excluded. The Liptak-Stouffer weighted Z-test for meta-analysis was implemented to maximize study inclusion and calculated separately for male and female cohorts.
Across 20 male cohorts, early adversity presaged antisocial outcomes more strongly for low-activity, relative to high- activity, MAOA genotype (p = .0044). Stratified analyses showed the interaction specific to maltreatment (p = .00000082) and robust to several sensitivity analyses. Across 11 female cohorts, MAOA did not interact with combined early life adversities, whereas maltreatment alone predicted antisocial behaviors preferentially, but weakly, in female subjects of high-activity MAOA genotype (p = .02).
We found common regulatory variation in MAOA to moderate effects of childhood maltreatment on male antisocial behaviors, confirming a sentinel finding in research on gene-environment interaction. An analogous, but less consistent, finding in female subjects warrants further investigation.
在一项关于基因-环境相互作用的开创性研究中，童年期虐待在携带 MAOA 启动子变异体的男性受试者中，对反社会行为的预测作用要强于转录效率较高的男性受试者。此后又进行了许多进一步的研究，包括对其他早期环境暴露和女性受试者的研究。在这里，我们报告了一项荟萃分析，该分析测试了 MAOA 基因型与童年逆境对主要为非临床样本中反社会结果的相互作用。
纳入了 27 项经过同行评审的、发表于 2012 年 8 月之前的英文文献，这些文献包含了虐待或其他家庭（如育儿、社会人口统计学）困难、MAOA 基因型、攻击和反社会行为指标以及基因型-环境相互作用的统计检验的指标。排除了法医和仅临床样本的研究、缺乏比例匹配对照受试者的临床队列或不特异于反社会行为的结果。实施了 Liptak-Stouffer 加权 Z 检验进行荟萃分析，以最大限度地纳入研究，并分别为男性和女性队列进行计算。
在 20 个男性队列中，早期逆境对低活性 MAOA 基因型的反社会结果预示作用更强，而对高活性 MAOA 基因型的反社会结果预示作用较弱（p=0.0044）。分层分析显示，这种相互作用是特异性的，仅与虐待有关（p=0.00000082），且对几种敏感性分析具有稳健性。在 11 个女性队列中，MAOA 与综合早期生活逆境没有相互作用，而虐待本身在高活性 MAOA 基因型的女性受试者中优先但微弱地预测了反社会行为（p=0.02）。
我们发现 MAOA 中的常见调节变异可调节童年期虐待对男性反社会行为的影响，证实了基因-环境相互作用研究中的一个重要发现。在女性受试者中发现的类似但不太一致的发现需要进一步研究。
