Gene-environment Interactions in Childhood Conduct Problems

项目摘要 著名学者的理论认为，心理社会适度的遗传影响（称为 基因-环境相互作用（GxE）是儿童行为的一个基本病因学组成部分 问题（CP;攻击性和违规行为）。即便如此，只有少数的实证研究 到目前为止，我们已经研究了这些过程。尽管这些开创性的研究提供了 为了支持CP中的GxE，需要进行额外的工作以更充分地充实它们的作用。比如说， 尽管在动物文献中有强有力的证据表明，正常范围的养育是一种 遗传对后代结果的影响的有效调节剂，迄今为止，大多数GxE研究 专注于极端环境病原体，如虐待儿童。因此，虽然他们 可能是重要的，我们对非虐待的作用知之甚少，但仍然功能失调，父母- 儿童关系在调节遗传对儿童CP的影响。保护性关系的作用 抑制儿童CP的遗传影响也在很大程度上被忽视，尽管它经常- 讨论了预防的意义。最后，很少有研究控制了基因-环境 相关性（rGE），或非随机暴露于特定的环境经验，一个基本的 在GxE研究中混淆。例如，如果消极的人际关系部分源于 CP共有的基因，然后在高水平的“环境”风险下增强遗传影响 可能是rGE过程的反映，而不是真正的GxE。拟议的研究旨在 解决这些限制，汇集了几个独特的元素，以整合遗传和 多层次分析儿童CP的心理社会机制。样品将 由500对社区为基础的同性双胞胎和他们的父母组成，这一设计使我们能够 评估保护性和风险性亲子关系的调节作用。分析将 顺序联合收割机定量和分子遗传GxE方法，以及控制 可能的rGE，从而克服了大多数方法学特定的限制和混淆。我们 因此，研究结合了最先进的思想和方法来检查CP中的GxE， 因此，有可能大大推进我们对儿童行为起源的理解 问题项目叙述 杰出的学者已经从理论上证明，基因-环境相互作用（GxE;心理社会 遗传影响的适度）代表了儿童行为起源的基本组成部分 问题（CP;攻击性和违反规则的行为），尽管我们对它们知之甚少。 该提案旨在全面探讨儿童CP中的GxE，评估其风险和 保护性亲子关系可能激活或抑制对儿童CP的遗传影响。等 研究结果最终将为更有效的个性化干预提供信息 旨在改善儿童CP。

PROJECT ABSTRACT Prominent scholars have theorized that psychosocial moderation of genetic influences (referred to as gene-environment interactions; GxE) represents a fundamental etiologic component in child conduct problems (CP; aggressive and rule-breaking behaviors). Even so, only a handful of empirical studies have examined these processes to date. Though these seminal studies have provided provocative support for GxE in CP, additional work is needed to more fully flesh out their role. For example, though there is strong evidence within the animal literature that normal-range parenting serves as a potent moderator of genetic influences on offspring outcomes, most GxE research to date has focused on extreme environmental pathogens such as child maltreatment. Thus, although they are likely to be important, we know very little about the role of non-abusive, but still dysfunctional, parent- child relationships in moderating genetic influences on child CP. The role of protective relationships in suppressing genetic influences for child CP has also been largely overlooked, despite its oft- discussed prevention implications. Finally, few studies have controlled for gene-environment correlations (rGE), or non-random exposure to particular environmental experiences, a fundamental confound in GxE research. For example, if negative interpersonal relationships stem in part from genes common to CP, then the potentiation of genetic influences at high levels of "environmental" risk could be a reflection of rGE processes, rather than true GxE. The proposed research seeks to address these limitations, bringing together several unique elements to integrate the genetic and psychosocial mechanisms underlying child CP across multiple levels of analysis. The sample will consist of 500 community-based, same-sex twin pairs and their parent(s), a design that enables us to evaluate the moderating roles of both protective and risky parent-child relationships. Analyses will sequentially combine both quantitative and molecular genetic GxE approaches, as well as control for possible rGE, thereby overcoming most methodology-specific limitations and confounds. Our investigation thus combines state-of-the-art ideas and methods to examine GxE in CP, and accordingly, has the potential to significantly advance our understanding of the origins of child conduct problems. PROJECT NARRATIVE Prominent scholars have theorized that gene-environment interactions (GxE; psychosocial moderation of genetic influences) represent a fundamental component of the origin of child conduct problems (CP; aggressive and rule-breaking behaviors), though we know little about them as of yet. This proposal intends to comprehensively explore GxE in child CP, evaluating how risky and protective parent-child relationships may activate or suppress genetic influences on child CP. Such findings should ultimately provide information for more effective individually-tailored interventions aimed at the amelioration of child CP.