The Genetic Epidemiology of COPD in Costa Rica

哥斯达黎加 COPD 的遗传流行病学

• 批准号: 7171840
• 负责人: Juan Carlos Celedon
• 金额: $ 70.13万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-04 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7171840
• 关键词: Accounting; Address; Affect; Age; Asthma; Bipolar Disorder; Bronchodilator Agents; Candidate Disease Gene; Case-Control Studies; Cause of Death; Chronic; Chronic Bronchitis; Chronic Obstructive Airway Disease; Collection; Complex; Costa Rica; Costa Rican; Data; Development; Disease; Epidemiology; Family; Founder Generation; General Population; Genes; Genetic; Genetic Determinism; Genome; Genome Scan; Genomics; Genotype; Goals; High Prevalence; Hispanics; IgE; Immigration; Individual; Life; Link; Lung diseases; Maps; Minority Groups; Molecular Biology; Numbers; Obstruction; Pathogenesis; Phenotype; Population; Province; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Relative (related person); Reporting; Research Design; Research Personnel; Risk Factors; Sample Size; Serum; Short Tandem Repeat; Single Nucleotide Polymorphism; Smoke; Smoker; Syndrome; Testing; Tobacco use; Uncertainty; United States; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; base; cigarette smoking; disease phenotype; disorder risk; genetic epidemiology; genetic linkage analysis; genetic pedigree; genetic risk factor; proband; trait

DESCRIPTION (provided by applicant): This application will examine the genetic factors that influence the development of chronic obstructive pulmonary disease (COPD) in Hispanics, a minority group at high risk for the disease. To this end, we will concentrate on a genetically isolated Hispanic population with a high prevalence of COPD living in the Central Valley of Costa Rica. To identify regions of the genome likely to contain genetic determinants of COPD-related phenotypes in this population, we will utilize a study design that entails collection of phenotypic and genotypic data on 30 large families of probands with moderate to severe COPD that have multiple individuals affected with smoking-related airflow obstruction, comprising 900 individuals from descendants of the Costa Rican Central Valley founder population. We will conduct a genome scan on these large pedigrees using short-tandem repeat (STR) markers and perform linkage analysis of six COPDrelated phenotypes: chronic bronchitis; airflow obstruction; FEV1; FEV1/FVC; bronchodilator responsiveness; and total serum IgE. Within genomic regions demonstrating linkage to COPD-related phenotypes in the genome scan, we will genotype narrowly spaced STR markers and test for linkage between these markers and COPD-related phenotypes. Within selected genomic regions, we will then test for association between single nucleotide polymorphisms (SNPs) in candidate genes and COPD-related phenotypes. By utilizing a family-based study design with a large sample size in a genetically isolated population, we should be able to address an important yet unstudied problem: the genetic influences on the expression of the COPD phenotype in Hispanics. This application will greatly contribute to our understanding of the pathogenesis of COPD in general, and among Hispanics in particular.

描述（由申请人提供）：本申请将研究影响西班牙裔慢性阻塞性肺疾病（COPD）发展的遗传因素，西班牙裔是该疾病高风险的少数群体。为此，我们将集中研究居住在哥斯达黎加中央谷的COPD高患病率的遗传隔离的西班牙裔人群。为了确定该人群中可能包含COPD相关表型遗传决定因素的基因组区域，我们将采用一种研究设计，该设计需要收集30个中重度COPD先证者大家族的表型和基因型数据，这些先证者有多个受吸烟相关气流阻塞影响的个体，包括900个来自哥斯达黎加中央谷创始人群体后代的个体。我们将使用短串联重复序列（STR）标记对这些大型家系进行基因组扫描，并对6种COPD相关表型进行连锁分析：慢性支气管炎、气流阻塞、FEV 1、FEV 1/FVC、支气管扩张剂反应性和血清总IgE。在基因组扫描中显示与COPD相关表型连锁的基因组区域内，我们将对窄间距STR标记进行基因分型，并检测这些标记与COPD相关表型之间的连锁。在选定的基因组区域内，我们将测试候选基因中的单核苷酸多态性（SNP）与COPD相关表型之间的关联。通过在遗传隔离人群中使用大样本量的以家族为基础的研究设计，我们应该能够解决一个重要但未研究的问题：西班牙裔COPD表型表达的遗传影响。这一应用将大大有助于我们了解COPD的发病机制，特别是在西班牙裔。