Examination of Genetic and GxE Effects in the Family and Community Health Studies

描述(申请人提供)：这项拨款申请的目的是将分子遗传学部分整合到目前资助的一项研究中，该研究旨在研究行为和环境因素对参与家庭和社区健康研究(FACHS)的非裔美国人(AA)受试者的心理健康和诊断状态的影响。拟议项目的生物材料将从来自爱荷华州和佐治亚州的771个非洲裔美国家庭的现有样本中收集，这些家庭被招募参加家庭和社区健康研究(FACHS)，所有这些家庭在1997年被招募到研究中时都有一个10至11岁的孩子。我们已经从这些妇女及其家人那里收集的数据为建立拟议的项目提供了丰富和广泛的纵向基础。除了敏感的背景测量之外，拟议使用以前经过验证的遗传标记减少了误差方差和机率大小写，为进行有针对性的分析奠定了基础，这些分析将理论模型扩展到重要的新方向。FACHS样本特别有价值，因为大量证据表明，遗传(G)、基因-环境相关性(RGE)和基因-环境(GxE)相互作用在影响各种与健康相关的结果(包括肥胖、高血压和抑郁症)的易感性方面都很重要。然而，到目前为止，这些研究主要集中在北欧族裔人口上，而忽略了其他族裔群体。此外，目前的样本提供了一个机会来检查再生障碍性贫血人群中以前未被识别的复原力因素。我们建议确定抑郁症和实质性疾病的具体风险和弹性因素。我们假设G、RGE和GxE的相互作用包括风险和弹性因素的一部分，这些因素负责改变这些女性对抑郁和物质使用的易感性。为了验证这一假设，我们将：1)从1076名受试者(初级和二级护理人员，其中大约200名二级护理人员是婚姻伴侣)收集DNA样本，2)对最佳验证的候选基因或基因座进行基因分型研究，3)对结果数据进行分析，以确定传递抑郁风险或弹性的因素或物质使用，4)然后在抑郁和物质使用的纵向、背景敏感的发展模型的背景下检查这些因素。作为这些研究的直接结果，我们将确定特定的G、RGE和GxE效应，这些效应在AA女性中提供保护或增加抑郁、药物使用和其他与健康相关的结果的风险。公共卫生相关性：这项赠款申请的目的是在目前得到资助的一项研究中增加分子遗传学部分，该研究旨在研究行为和环境因素对参与家庭和社区健康研究(FACHS)的非裔美国人(AA)受试者的心理健康和诊断状态的影响。

DESCRIPTION (provided by applicant): The purpose of this grant application is to integrate a molecular genetics component to a currently funded study of the effects of behavioral and environmental factors on psychological well-being and diagnostic status of African-American (AA) subjects participating in the Family and Community Health Study (FACHS). The biomaterial for the proposed project will be collected from an existing sample of 771 African American families from Iowa and Georgia who were recruited to participate in the Family and Community Health Study (FACHS), all of whom had a child who was 10 to 11 years of age at the time of recruitment into the study in 1997. The data we have already collected from these women and their families provides a rich and extensive longitudinal foundation upon which to build the proposed project. The proposed use of previously validated genetic markers in addition to sensitive measures of context reduces error variance and capitalization on chance, setting the stage for well targeted analyses that extend theoretical models in important new directions. The FACHS sample is particularly valuable because a large body of evidence has accumulated that demonstrates that both genetic (G), gene-environment correlations (rGE) and gene-environment (GxE) interactions are important in influencing vulnerability to a wide variety health-related outcomes including obesity, hypertension and depression. To date, however, these studies have largely focused on populations of northern European ethnicity to the exclusion of other ethnic groups. In addition, the current sample provides an opportunity to examine previously unrecognized resilience factors in the AA population. We propose to identify specific risk and resilience factors for depression and substance. We hypothesize that G, rGE, and GxE interactions comprise a portion of the risk and resiliency factors responsible for altering vulnerability to depression and substance use in these women. To test this hypothesis we will: 1) collect DNA samples from 1076 subjects (primary and secondary care givers with approximately 200 of the secondary care givers being marital partners), 2) conduct genotyping studies of the best validated candidate genes or loci, 3) conduct analyses of the resulting data to identify factors conveying risk or resilience to depression or substance use, and 4) then examine these factors in the context of longitudinal, contextually sensitive, developmental models of depression and substance use. As a direct result of these studies, we will determine specific G, rGE and GxE effects that either confer protection or confer increased risk for depression, substance use and other health related outcomes among AA women. PUBLIC HEALTH RELEVANCE: The purpose of this grant application is to add a molecular genetics component to a currently funded study of the effects of behavioral and environmental factors on psychological well-being and diagnostic status of African-American (AA) subjects participating in the Family and Community Health Study (FACHS).