Exome array analysis of pulmonary function in smokers with and without chronic obstructive pulmonary disease (COPD)

COPD;genetics;lung function;GWAS;exome array;not listed

Parker, Margaret M.Mathias, Rasika ;

Johns Hopkins University

关键词: COPD;    genetics;    lung function;    GWAS;    exome array;    not listed;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/39390/PARKER-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease characterized by airflow restriction and decreased lung function. It is the 3rd leading cause of death worldwide, accounting for approximately 3 million deaths in 2010. It is diagnosed using spirometric measurements, including the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). These measures reflect the severity of airway obstruction and predict population morbidity and mortality. The primary environmental cause of COPD is cigarette smoking, but genetics also play a role in individual susceptibility and disease progression. Genome-wide association studies (GWAS) have identified over 30 loci associated with lung, but together the identified variants can only explain a small proportion of the variation in spirometric measures and a small proportion of the estimated heritability. We hypothesized: 1) rare functional variation also affects lung function; and 2) genetic variation (both common and rare) affects longitudinal changes in lung function. This dissertation tests these hypotheses using data from the COPDgene study, a large multicenter study of current and former smokers.