Gene-environment Interactions in Childhood Conduct Problems

描述（由研究者提供）：著名学者认为，遗传影响的社会心理调节（称为基因-环境相互作用; GXE）代表了儿童行为问题（CP;攻击性和违规行为）的基本病因组成部分。即便如此，迄今为止，只有少数实证研究考察了这些过程。虽然这些开创性的研究为GxE在CP中提供了挑衅性的支持，但还需要更多的工作来更充分地充实它们的作用。例如，尽管在动物文献中有强有力的证据表明，正常范围的养育是对后代结果遗传影响的有力调节剂，但迄今为止，大多数GxE研究都集中在极端环境病原体上，如虐待儿童。因此，尽管它们可能很重要，但我们对非虐待性的，但仍然功能失调的亲子关系在调节儿童CP遗传影响中的作用知之甚少。保护性关系在抑制儿童CP遗传影响方面的作用也在很大程度上被忽视了，尽管其经常被讨论的预防意义。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，这是GxE研究中的一个基本混淆。例如，如果消极的人际关系部分源于CP共有的基因，那么在高水平的“环境”风险下遗传影响的增强可能是rGE过程的反映，而不是真正的GxE。拟议的研究旨在解决这些局限性，汇集了几个独特的元素，以整合多个层次分析儿童CP的遗传和心理社会机制。样本将由500个社区为基础的同性双胞胎和他们的父母组成，这种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。分析将依次结合联合收割机定量和分子遗传GxE方法，以及控制可能的rGE，从而克服大多数方法学特定的限制和混淆。因此，我们的调查结合了国家的最先进的思想和方法来检查GXE在CP，因此，有可能显着推进我们的理解的起源儿童行为问题。著名学者已经提出理论，认为基因-环境相互作用（GxE;遗传影响的社会心理调节）是儿童行为问题（CP;攻击性和违规行为）起源的基本组成部分，尽管我们对它们知之甚少。本申请旨在全面探讨儿童CP的GxE，评估风险和保护性亲子关系如何激活或抑制对儿童CP的遗传影响。这些研究结果最终应提供信息，更有效的个性化的干预措施，旨在改善儿童CP。

DESCRIPTION (provided by investigator): 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 application 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.