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

描述（由申请人提供）：本资助申请的目的是将分子遗传学成分整合到目前资助的研究中，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）的非洲裔美国人（AA）受试者的心理健康和诊断状况的影响。将从来自爱荷华州和格鲁吉亚的771个非裔美国人家庭的现有样本中收集拟议项目的生物材料，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年招募参加研究时都有一个10至11岁的孩子。我们已经从这些妇女及其家庭收集的数据提供了一个丰富而广泛的纵向基础，在此基础上建立拟议的项目。除了敏感的背景措施，建议使用以前验证的遗传标记减少了误差方差和资本化的机会，为有针对性的分析，扩展理论模型在重要的新方向的阶段。FACHS样本特别有价值，因为已经积累了大量证据，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健康相关结果（包括肥胖，高血压和抑郁症）的脆弱性方面非常重要。然而，迄今为止，这些研究主要集中在北方欧洲族裔的人口，排除了其他族裔群体。此外，目前的样本提供了一个机会，以检查以前未被认识到的弹性因素在AA人口。我们建议确定抑郁症和物质的特定风险和弹性因素。我们假设，G，rGE和GxE的相互作用包括一部分的风险和弹性因素负责改变这些妇女的抑郁症和物质使用的脆弱性。为了验证这个假设，我们将：1）从1076名受试者中收集DNA样本（初级和二级护理提供者，其中大约200名二级护理提供者是婚姻伴侣），2）对最佳验证的候选基因或位点进行基因分型研究，3）对所得数据进行分析以识别传递抑郁或物质使用的风险或恢复力的因素，4）然后在纵向的、情境敏感的、抑郁和物质使用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的影响，无论是提供保护或增加风险的抑郁症，物质使用和其他健康相关的结果AA妇女。公共卫生相关性：这项拨款申请的目的是增加一个分子遗传学组成部分，目前资助的研究行为和环境因素对心理健康和诊断状态的非洲裔美国人（AA）的主题参与家庭和社区健康研究（FACHS）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).