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: 8336539
• 负责人: Stephanie London
• 金额: $ 27.88万
• 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/8336539
• 关键词: Acute; Adult; Affect; African American; 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; Data Set; Development; Diet; Disease; Drops; Enrollment; Environment; Environmental Exposure; Environmental Risk Factor; Environmental Tobacco Smoke; Epidemiology; Etiology; European; Exposure to; Extramural Activities; Farming environment; Funding; Genes; Genetic; Genetic Predisposition to Disease; Genomics; Genotype; Goals; Health; Heart; Heart Diseases; Inflammatory Response; Inhalation Toxicology; Iowa; Lead; Life Cycle Stages; Lung diseases; Manuscripts; Measures; Mediating; Meta-Analysis; Methods; 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; Venous; Woman; Work; base; cohort; disease phenotype; exposed human population; farmer; follow-up; gene environment interaction; genome wide association study; genome-wide; interest; longitudinal analysis; malignant breast neoplasm; named group; next generation; novel; ozone exposure; pollutant; pulmonary function; research study; respiratory; response; trafficking; trait

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. In the past year we have published on the relationship between traffic related air pollution and venous thromboembolic disease in ARIC. 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. All but one have now been replicated by other groups. We are participating in an extramurally funded project to use next generation sequencing to narrow down the causal SNPs involved in the associations that we have identified from GWAS. In the past year we have collaborated with a European consortium called SpiroMeta to do large meta-analyses. In a meta-analysis of the same pulmonary function traits we have identified an additional 16 novel loci. We are completing a manuscript on meta-analysis of COPD in CHARGE and SpiroMeta. We are also examining genome-wide interactions with smoking in relation to pulmonary function. This work lead to a collaborative methods paper with extramural investigators. We are also working on longitudinal analysis of pulmonary function which has involved application of novel methods in the GWAS setting. 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 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. Enrollment is nearly complete 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。我们在该数据集中添加了交通暴露评估，并检查了与呼吸和心血管终点相关的交通相关空气污染的替代指标。去年，我们在 ARIC 中发表了有关交通相关空气污染与静脉血栓栓塞性疾病之间关系的文章。 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。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。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。 我们正在参与一个外部资助的项目，利用下一代测序来缩小我们从 GWAS 中确定的关联所涉及的因果 SNP 的范围。 去年，我们与一家名为 SpiroMeta 的欧洲联盟合作进行了大型荟萃分析。在对相同肺功能特征的荟萃分析中，我们发现了另外 16 个新位点。我们正在 CHARGE 和 SpiroMeta 中完成一份关于 COPD 荟萃分析的手稿。我们还在研究吸烟与肺功能之间的全基因组相互作用。这项工作导致了与校外研究人员合作的方法论文。我们还致力于肺功能的纵向分析，其中涉及在 GWAS 环境中应用新方法。我们还与一个名为 CARe 的联盟合作，检查 ARIC 和其他队列中非裔美国人的 GWAS 数据。 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。这项研究的招募工作即将完成。