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

基本信息

批准号：
8553692
负责人：
Stephanie London
金额：
$ 28.71万
依托单位：
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
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/8553692
关键词：
Acute Adult Affect Aging Agriculture Air Air Pollution Airway Resistance Allergic Disease Annual Reports Asthma Atherosclerosis Breathing Candidate Disease Gene Cardiovascular Diseases Cardiovascular system Chronic Obstructive Airway Disease Collaborations Communities Data Data Quality Development Diet Drops Enrollment Environment Environmental Exposure Environmental Risk Factor Environmental Tobacco Smoke Epidemiology Etiology European Exposure to Farming environment Funding Genes Genetic Genetic Predisposition to Disease Genets Genome Genomics Genotype Goals Health Heart Heart Diseases Inflammatory Response Inhalation Toxicology Iowa Joints Life Cycle Stages Lung diseases Measures Mediating Meta-Analysis Mus National Institute of Environmental Health Sciences Non-Malignant North Carolina Obese Mice Obesity Occupational Occupational Exposure Outcome Ozone Paper Pesticides Phenotype Play Population Predisposition Publishing Pulmonary Function Test/Forced Expiratory Volume 1 Questionnaires Research Research Personnel Resistance Resources Risk Role Sister Smoking Spirometry Spouses Staging Time Variant Woman Work base cohort disease phenotype exome exposed human population farmer follow-up gene environment interaction genome wide association study genome-wide interest longitudinal analysis malignant breast neoplasm mouse model named group next generation novel ozone exposure pollutant pulmonary function research study respiratory response trafficking

项目摘要

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 have used the genome wide association genotyping in ARIC to look for novel genes associated with pulmonary function and chronic obstructive pulmonary disease (COPD). In 2009, 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 (Hancock et al. Nat Genet 2009). In our CHARGE meta-analysis, we identified eight novel loci related to pulmonary function. All but one have now been replicated by other groups. We subsequently developed a collaborated with a European consortium (SpiroMeta) to expand our work. We have published joint consortium papers on pulmonary function (Soler Artigas et al. Nat Genet 2011) and COPD (Wilk et al. AJRCCM 2012). We have submitted a paper on genome wide interaction with smoking in relation to pulmonary function and are working on analysis of longitudinal change in pulmonary function and additional analyses. 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 are doing 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. We have completed enrollment for this study.

为了研究遗传和环境因素及其相互作用对成人呼吸健康的影响，我们建立了一些高质量的人口资源。我们一直在与外部资助的社区动脉粥样硬化风险 (ARIC) 研究合作，以检查成人呼吸系统健康的遗传和环境因素。 ARIC 研究是 1987 年至 1989 年间在美国四个社区聚集的 16,000 名成年人的队列。 ARIC 拥有丰富的详细心血管和呼吸表型。我们在 ARIC 中使用全基因组关联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。 2009 年，我们在 CHARGE 联盟（基因组流行病学心脏和衰老研究队列）内组建了一个肺功能分析小组，其中包括其他几个具有全基因组关联基因分型和肺功能数据的队列（Hancock 等人 Nat Genet 2009）。在我们的 CHARGE 荟萃分析中，我们确定了八个与肺功能相关的新位点。除其中一项外，所有其他研究现在都已被其他研究组复制。随后，我们与欧洲联盟 (SpiroMeta) 建立了合作关系以扩展我们的工作。我们发表了关于肺功能（Soler Artigas 等人 Nat Genet 2011）和慢性阻塞性肺病（Wilk 等人 AJRCCM 2012）的联合论文。我们已经提交了一篇关于吸烟与肺功能相关的全基因组相互作用的论文，并正在致力于分析肺功能的纵向变化和其他分析。在过去的几年里，我一直与 Jane Hoppin 和 NIEHS 和 NCI 的其他人合作，在农业健康研究 (AHS) 中研究与哮喘和慢性阻塞性肺病表型相关的农业因素，该研究由爱荷华州的一大群农民及其配偶组成。北卡罗来纳州。迄今为止，我们根据非常简单的问卷结果得出了许多有趣的发现。今年我们继续在新论文中扩展这些观察结果。为了跟进这些观察结果，我们正在进行一项新的研究，该研究在单独的年度报告 ES102385-01 中进行了描述。另一个群体是 NIEHS 姐妹研究。 NIEHS 队列已招募了 50,000 名患有乳腺癌的女性姐妹。我在调查问卷中添加了非恶性呼吸系统疾病问题，目的是在该队列成熟时检查与呼吸系统疾病相关的基因-环境相互作用。该队列每年都会得到随访。我与 EPA-UNC 人类暴露设施的研究人员合作，开展了一项研究，以跟进最近的实验工作，结果表明，肥胖小鼠对臭氧的呼吸反应比瘦小鼠更强。这项工作还延续了我们最近的发现，即 BMI 较高的受试者因急性臭氧暴露而导致肺功能 (FEV1) 下降幅度更大（Bennett 等人，吸入毒理学，2007 年）。我们开展了一项实验研究，将中心性肥胖和偏瘦的女性暴露在臭氧中，并测量肺量测定、空气阻力、气道高反应性和对暴露的炎症反应。我们已经完成了这项研究的注册。