GENOMICS AND PHARMACOGENOMICS OF SYMPTOMS IN ASTHMA

哮喘症状的基因组学和药物基因组学

• 批准号: 8517208
• 负责人: KELAN G TANTISIRA
• 金额: $ 42.3万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-27 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8517208
• 关键词: Accounting; Adrenal Cortex Hormones; Affect; American; American Lung Association; Asthma; Behavioral; Breathing; Caring; Characteristics; Child; Childhood Asthma; Classification; Clinical; Clinical Research; Clinical Trials; Cognitive; Cohort Studies; Complex; DNA; Data; Disease; Drug Formulations; Dyspnea; Education; Enrollment; Environmental Risk Factor; Frequencies; Future; Genetic; Genetic Markers; Genomics; Genotype; Goals; Guidelines; Health; Health Care Costs; Healthcare; Hospitalization; Impairment; Indium; Individual; Intervention; Investigation; Lead; Link; Methods; Modeling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Obstruction; Outcome; Patient Self-Report; Patients; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Phenotype; Physiological; Play; Population; Population Programs; Predisposition; Provider; Quality of life; Reporting; Research; Respiratory physiology; Risk; Schools; Self Assessment; Severities; Socioeconomic Factors; Specific qualifier value; Symptoms; Testing; Time; United States; Variant; Wheezing; airway inflammation; base; clinical phenotype; cohort; cost; design; experience; genetic association; genetic variant; genome wide association study; genome-wide; high risk; improved; novel; predictive modeling; primary outcome; prognostic; programs; psychologic; psychosocial; response; socioeconomics; symptom management; symptomatic improvement; therapeutic development; treatment response

DESCRIPTION (provided by applicant): Asthma affects over 300 million individuals worldwide. Asthma symptoms are tightly correlated with overall quality of life; persistent symptoms resulting in poor asthma control leads to disproportionate morbidity and cost. Genome-wide association studies have been extensively applied to the study of asthma susceptibility and lung function in asthma, but have yet to be applied in a systematic fashion to studies of self-reported symptoms in asthma. The major goal of this project is to thoroughly investigate the genetic origins of asthma symptoms via genome-wide association study. To accomplish this, we have specified three related but independent aims. The first aim evaluates data from over 500,000 genetic markers for their association with symptoms as reported at the time of enrollment into a clinical trial or clinical cohort. The markers with the strongest evidence for association will be tested for replication in independent clinical cohorts. The second aim seeks to understand the genetic basis for response of symptoms to drug treatment (pharmacogenetics). Instead of analyzing baseline symptoms, the change in symptoms as a response to inhaled corticosteroid medications will be the primary outcome phenotype for this aim, which will also use genome-wide association testing and replication methods. Our final aim will be to develop a model, using both genotype and phenotypic characteristics, including demographic, psychosocial, and behavioral factors, to predict who is at greatest risk of developing persistent symptoms in asthma. Dozens to hundreds of genetic markers will be used to develop these predictive tests, which will be formulated and validated for both persistent symptoms and treatment response of symptoms. We believe that these findings will uncover the genetic basis for symptoms in asthma and lead to novel interventions to predict and alleviate this major health care problem.

描述（由申请人提供）：哮喘影响全球超过3亿人。哮喘症状与整体生活质量密切相关;持续的症状导致哮喘控制不佳，导致不成比例的发病率和成本。全基因组关联研究已广泛应用于哮喘易感性和哮喘肺功能的研究，但尚未系统地应用于哮喘自我报告症状的研究。本项目的主要目的是通过全基因组关联研究来彻底调查哮喘症状的遗传起源。为了实现这一目标，我们确定了三个相互关联但又相互独立的目标。第一个目标是评估来自超过50万个遗传标记的数据，以确定它们与临床试验或临床队列招募时报告的症状的关联。将在独立的临床队列中检测具有最强相关性证据的标志物的重复性。第二个目标是了解药物治疗后症状反应的遗传基础（药物遗传学）。而不是分析基线症状，症状的变化作为吸入性皮质类固醇药物的反应将是这一目标的主要结果表型，这也将使用全基因组关联测试和复制方法。我们的最终目标将是开发一个模型，使用基因型和表型特征，包括人口统计学，心理社会和行为因素，预测谁是最大的风险发展为哮喘持续症状。数十到数百个遗传标记将用于开发这些预测性测试，这些测试将针对持续症状和症状的治疗反应进行制定和验证。我们相信，这些发现将揭示哮喘症状的遗传基础，并导致新的干预措施来预测和缓解这一主要的卫生保健问题。