Genetics and Environment in Adult Respiratory, Allergic and Cardiac disease

成人呼吸系统、过敏和心脏病的遗传学和环境

• 批准号: 8148999
• 负责人: Stephanie London
• 金额: $ 22.57万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8148999
• 关键词: Adult; Allergic; Environment; Genetic; Heart Diseases; respiratory

To investigate the effects of genetic and environmental factors, and their interactions, on respiratory health in adults we have established several high-quality population resources. We have been working with the extramurally funded cohort, the Atherosclerosis Risk in Communities (ARIC) study to examine both genetic and environmental factors in adult respiratory health. The ARIC study is a cohort of 16,000 adults assembled from 1987-1989 in four US communities. ARIC has a wealth of detailed cardiovascular and respiratory phenotypes. We added the assessment of exposure to traffic to this dataset and have examined this surrogate of traffic related air pollution in relation to respiratory and cardiovascular endpoints. We have used the genome wide association genotyping in ARIC to look for novel genes associated with pulmonary function and chronic obstructive pulmonary disease (COPD). We formed a pulmonary function analysis group within the CHARGE consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology) which includes several other cohorts with genome wide association genotyping and pulmonary function data. In our CHARGE meta-analysis, we identified eight novel loci related to pulmonary function. Most of these replicated in a second consortium (SpiroMeta). Two others have subsequently been replicated in published studies. We are working on meta-analysis of COPD in CHARGE. We are also examining genome-wide interactions with smoking in relation to pulmonary function. This has involved collaborations with methodologists to extend existing methods for GWAS and meta-analysis to address our needs. We are also working on longitudinal analysis of pulmonary function. We also also working with a consortium called CARe for examination of the GWAS data from African-Americans in ARIC and other cohorts. Over the past several years, I have been collaborating with Jane Hoppin and others at NIEHS and NCI to examine agricultural factors in relation to asthma and COPD phenotypes in the Agricultural Health Study (AHS), a large cohort of farmers and their spouses in Iowa and North Carolina. To date, we have had a number of interesting findings based on very simple questionnaire outcomes. We continued to expand these observations in new papers this year. To follow-up on these observations, we have started a new study which is described in a separate annual report - ES102385-01. Another population is the NIEHS Sister Study. This NIEHS cohort has enrolled 50,000 sisters of women with breast cancer. I have added nonmalignant respiratory disease questions to the questionnaire with the aim of examining gene-environment interaction in relation to respiratory disease in this cohort as it matures. The cohort is being followed up annually. In collaboration with investigators at the EPA-UNC Human Exposure Facility, I have established a study to follow-up on recent experimental work showing that obese mice have greater respiratory response to ozone than lean mice. This work also follows up our recent finding that subjects with higher BMI have greater drop in pulmonary function (FEV1) in response to acute ozone exposure(Bennett et al., Inhalation Toxicology, 2007). We have established an experimental study where we expose centrally obese and lean women to ozone and measure spirometry, air resistance, airway hyperresonsiveness and inflammatory responses to the exposure. Enrollment is approximately 75% complete for this study.

为了研究遗传和环境因素及其相互作用的影响，我们已经建立了几种高质量的人口资源。 我们一直在与外部资助的队列（社区中的动脉粥样硬化风险（ARIC）研究）合作，以检查成人呼吸健康的遗传和环境因素。 ARIC研究是从1987 - 1989年在美国四个社区组成的16,000名成年人组成的队列。 ARIC拥有大量详细的心血管和呼吸表型。我们添加了对该数据集的流量暴露的评估，并检查了与呼吸道和心血管终点有关的交通相关空气污染的替代。 我们已经在ARIC中使用了基因组广泛的基因分型来寻找与肺功能和慢性阻塞性肺疾病（COPD）相关的新基因。我们在电荷联盟（基因组流行病学中的心脏和衰老研究）中形成了一个肺功能分析组，其中包括其他几个具有基因组宽的缔合基因分型和肺功能数据的同类。在我们的电荷荟萃分析中，我们确定了与肺功能相关的八个新型基因座。其中大多数在第二个财团（Spirometa）中复制。随后在已发表的研究中复制了另外两个。 我们正在负责COPD的荟萃分析。我们还正在研究与吸烟有关肺功能的全基因组相互作用。这涉及与方法学家的合作，以扩展GWAS和荟萃分析的现有方法以满足我们的需求。我们还在研究肺功能的纵向分析。我们还与一个称为Care care the ARIC和其他同伙的GWAS数据的财团合作。 在过去的几年中，我一直与Niehs和NCI的Jane Hoppin和其他人合作研究农业健康研究（AHS）中与哮喘和COPD表型有关的农业因素，这是爱荷华州和北卡罗来纳州的大量农民及其配偶。迄今为止，我们基于非常简单的问卷结果有许多有趣的发现。今年，我们继续在新论文中扩大这些观察结果。为了跟进这些观察结果，我们已经开始了一项新的研究，该研究在另一份年度报告-ES102385-01中进行了描述。 另一个人群是Niehs姊妹研究。这个NIEHS队列已招募了50,000个乳腺癌女性姐妹。我已经在问卷中添加了非恶性呼吸道疾病问题，目的是检查该队列中与呼吸道疾病有关的基因环境相互作用。每年都会跟进该队列。 与EPA-INC人类暴露设施的研究人员合作，我建立了一项研究，以跟进最近的实验工作，表明肥胖小鼠对臭氧的呼吸反应比瘦小鼠更大。这项工作还遵循了我们最近的发现，即BMI较高的受试者响应急性臭氧暴露时的肺功能下降（FEV1）（FEV1）（Bennett等人，吸入毒理学，2007年）。我们已经建立了一项实验研究，我们将中央肥胖和瘦女性暴露于臭氧，并测量肺活量法，空气阻力，气道高感和对暴露的炎症反应。这项研究的入学人数约为75％。