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

描述（由申请人提供）：本RO1申请寻求为期五年的支持，以对现有社区样本进行分子遗传学研究，参与者超过2,400人，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）。本提案的主要目的是利用加权的、基于家庭的全基因组关联研究（GWAS）来评估遗传(G)、环境(E)和基因与环境相互作用（GxE）对一系列核心人格属性的影响，这些核心人格属性与一系列重要的发育结果有关。具体来说，我们建议研究遗传和环境对行为去抑制（BD）和气质恢复（DR）潜在特征的影响。双相障碍反映了对令人兴奋的食欲刺激的过度追求，对危险行为的厌恶后果的漠视，以及对他人缺乏关心的攻击行为的倾向。相反，DR反映了情绪稳定性、人际敏感性、自信和自我导向，以应对与成就相关的挑战。这些特征早在幼儿时期就出现了，并在整个生命过程中继续产生重要的发展影响。特别是，这些属性会影响个人是否发展出特定的能力和牢固的人际关系，或者个人是否会出现严重损害其健康和福祉的问题，如吸毒、犯罪和从事危险行为。为了解决这些重要的问题，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目标是早期青少年，并从那时起继续进行年度评估。G2组成员现在的平均年龄为33岁。研究中的每一代人都经过了几年的评估，使用的测量策略既广泛（即涵盖个人和社会特征的多个领域）又密集（即采用多信息方法，包括自我报告、其他家庭成员报告、教师报告、训练有素的观察员评分、学校记录和公共记录）。申请的资金将用于收集FTP参与者的DNA和基因型。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，该样本中独特的家庭结构包括遗传信息丰富的父母-后代（G1-G2和G2- g3）和兄弟姐妹关系（G2），这将是基于家庭的关联测试（FBAT）方法的理想选择。

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.