A Genetic Study of Personal Traits that Promote or Inhibit Individual Well-Being

描述（由申请人提供）：本RO 1申请寻求五年的支持，以进行一项分子遗传学研究，研究对象为现有的2,400多名参与者，包括500名队列成员（G2目标）、他们的近亲兄弟姐妹、他们的父母（G1）、他们的浪漫伴侣和他们最大的亲生子女（G3）。该提案的广泛目标是评估遗传（G），环境（E）和基因x环境相互作用（GxE）对一组核心人格属性的影响，这些属性与一系列重要的发展结果有关，使用加权的，基于家庭的全基因组关联研究（GWAS）。具体来说，我们建议检查遗传和环境的贡献的潜在特征的行为去抑制（BD）和性格韧性（DR）。BD反映了过度追求令人兴奋的食欲刺激，忽视危险行为的不良后果，以及缺乏对他人的关注的攻击性行为倾向。相反，DR反映了情绪稳定性，人际敏感性以及应对与成就相关的挑战的自信和自我导向。这些属性早在幼儿时期就存在，并在整个生命过程中继续产生重要的发展后果。特别是，这些属性影响个人是否发展特定的能力和强大的人际关系，或者个人是否发展出可能严重损害其健康和福祉的问题，例如参与物质，犯罪和从事危险行为。 为了解决这些重要问题，我们将使用来自家庭过渡项目（FTP）的现有数据以及作为拟议研究的一部分收集的遗传信息。FTP于1989年启动，当时G2的目标是早期青少年，并从那时起继续进行年度评估。G2队列成员现在的平均年龄为33岁。研究中的每一代都使用广泛的测量策略（即，覆盖个人和社会特征的多个领域）和密集（即，采用多信息源方法，包括自我报告、其他家庭成员报告、教师报告、受过训练的观察员的评级、学校记录和公共记录）。所要求的资金将用于收集DNA和基因型的FTP参与者。基因型信息将与现有的背景和表型数据档案相结合，以评估遗传和环境对BD和DR的影响。特别是，该样本中独特的家族结构包括遗传信息丰富的亲子关系（G1-G2和G2-G3）和兄弟姐妹关系（G2），这对于基于家族的关联检验（FBAT）方法是理想的。 公共卫生相关性：目前研究的目标是增加对遗传和环境因素的理解，这些因素塑造了与整个生命周期中适应不良和适应性发展结果相关的特定个人属性。成就动机、人际敏感和积极的身份等属性倾向于促进成功的适应，而与行为去抑制相关的属性则与物质使用、犯罪、健康风险和人际关系困难相关。这些特征的遗传和环境基础的澄清有可能带来巨大的公共卫生利益。事实上，拟议研究的结果应该提供具体的见解，可以为旨在促进人类健康发展和减少精神病理学和问题行为的预防和治疗工作提供信息。

DESCRIPTION (provided by applicant): This RO1 application seeks five years of support to conduct a molecular genetics study of an existing community-based sample of over 2,400 participants including 500 cohort members (G2 targets), their close- aged siblings, their parents (G1), their romantic partners, and their oldest biological child (G3). The broad objective of this proposal is to evaluate genetic (G), environmental (E), and gene x environment interaction (GxE) effects on a set of core personality attributes that are linked to a host of important developmental outcomes using a weighted, family-based genome-wide association study (GWAS). Specifically, we propose to examine genetic and environmental contributions to the latent traits of Behavioral Disinhibition (BD) and Dispositional Resilience (DR). BD reflects excessive pursuit of exciting appetitive stimuli, disregard for the aversive consequences of risky behaviors, and a tendency to engage in aggressive acts that demonstrate a lack of concern for others. Conversely, DR reflects emotional stability, interpersonal sensitivity, and a self-confident and self-directed orientation to meeting achievement-related challenges. These attributes are present as early as toddlerhood and continue to have important developmental consequences across the life course. In particular these attributes influence whether individuals develop specific competencies and strong interpersonal relationships or whether individuals develop problems that can significantly impair their health and well-being such as involvement with substances, crime, and engaging in risky behaviors. To address these important questions, we will use both existing data from the Family Transitions Project (FTP) as well as genetic information to be collected as part of the proposed study. The FTP was initiated in 1989 when the G2 targets were early adolescents and has continued with annual assessments since that time. The G2 cohort members now average 33 years of age. Each generation in the study has been assessed over a several year period of time using a measurement strategy that is both extensive (i.e., covers multiple domains of personal and social characteristics) and intensive (i.e., employs a multi- informant approach that includes self-reports, other family member reports, teacher reports, ratings by trained observers, school records and public records). Requested funds will be used to collect DNA and genotype the FTP participants. Genotypic information will be combined with the existing archive of contextual and phenotypic data to evaluate genetic and environmental influences on BD and DR. In particular, the unique family structures in this sample include genetically-informative parent-offspring (both G1-G2 and G2-G3) and sibling relationships (G2) which will be ideal for Family-Based Association Test (FBAT) methods. PUBLIC HEALTH RELEVANCE: The goal of the current study is to increase understanding of genetic and environmental factors that shape specific personal attributes that are linked with both maladaptive and adaptive developmental outcomes across the life span. Attributes such as achievement motivation, interpersonal sensitivity, and a positive identity tend to promote successful adaptation, whereas attributes linked with behavioral disinhibition are associated with substance use, crime, health risks, and interpersonal difficulties. The clarification of the genetic and environmental underpinnings of these traits has the potential for enormous public health benefits. Indeed, results from the proposed study should provide specific insights that can inform prevention and treatment efforts designed to promote healthy human development and to reduce psychopathology and problem behaviors.