Genetic Admixture and Pulmonary Function Decline

描述(由申请人提供)：肺功能下降随着年龄的增长而下降；然而，下降的速度因种族/民族和性别而异。在美国，与白人和墨西哥裔美国人相比，非裔美国人的肺功能低下最严重。肺功能下降是遗传因素和环境因素共同作用的复杂疾病。非洲裔美国人被认为是混血儿，他们拥有不同比例的非洲人、美洲印第安人和欧洲人的祖先。非洲裔美国人的混合血统在复杂特征的流行病学研究中提供了独特的机会，并可能有助于解开疾病易感性中基因与环境的相互作用。这项提案的目标是确定与非裔美国人肺功能下降和肺功能下降相关的遗传因素，并检查观察到的遗传关联是否因接触烟草烟雾而改变。这项研究将利用健康、老龄化和身体成分研究中现有的基因分型和流行病学数据，这是一项大型纵向队列研究，旨在调查老年人口的功能衰退。将使用祖先信息标记估计遗传祖先，并将研究遗传祖先与肺功能减退和肺功能下降之间的联系。这项研究将对肺功能的遗传学以及基因-环境交互作用对非裔美国人肺功能的种族/民族差异的影响提供重要的见解。提出了以下具体目标： 目的1)确定基因血统与肺功能减退和肺功能随时间的下降之间的关系。目的2)进行混合型作图以确定与肺功能减退和肺功能减退相关的基因座。目的3)研究混合剂是否改变了烟草烟雾暴露与肺功能之间的关系。总结：老年人有很高的并存疾病的患病率，肺气流受限往往没有被认识到。识别影响肺功能下降的基因可以识别药物治疗的新靶点，并导致重要临床测试的发展。这项研究试图找到欧洲或非洲起源的基因，这些基因会导致非裔美国人呼吸健康的变化。

DESCRIPTION (provided by applicant): Pulmonary function decline occurs with advanced age; however, the rate of decline varies by race/ethnicity and sex. In the United States, lower lung function is greatest among African Americans compared to whites and Mexican Americans. Pulmonary function decline is a complex disease resulting from the interaction of genetic and environmental factors. African Americans are considered to be admixed and share varying proportions of African, Amerindian and European ancestry. The mixed ancestry of African Americans provides unique opportunities in epidemiologic studies of complex traits and may be useful in untangling gene-environment interactions in disease susceptibility. The goal of this proposal is to identify genetic factors associated with reduced pulmonary function and pulmonary function decline among African Americans and examine whether observed genetic associations are modified by tobacco smoke exposure. This research will leverage existing genotyping and epidemiologic data from the Health, Aging, & Body Composition Study, a large longitudinal cohort study examining functional decline in older populations. Genetic ancestry will be estimated using ancestry informative markers and associations between genetic ancestry and reduced lung function and lung function decline will be examined. This research will provide important insight into the genetics of lung function and the impact of gene-environment interactions on racial/ethnic differences in lung function among African Americans. The following specific aims are proposed: Aim 1) To determine the association between genetic ancestry and reduced lung function and lung function decline over time. Aim 2) To perform admixture mapping to identify genetic loci associated with reduced lung function and lung function decline. Aim 3) To examine whether admixture modifies the association between tobacco smoke exposure and lung function. Lay Summary: Older adults have a high prevalence of comorbid diseases and limitations in lung airflow are often unrecognized. Identification of genes that affect pulmonary decline can identify new targets for drug treatments and lead to the development of important clinical tests. This study seeks to find genes of European or African origin that cause changes in the respiratory health of African Americans.