Genome-Wide Association Analysis of Body Mass in Chronic Obstructive Pulmonary Disease
Year: 2010
Type: article
Study design: Observational Study
Abstract: Cachexia, whether assessed by body mass index (BMI) or fat-free mass index (FFMI), affects a significant proportion of patients with chronic obstructive pulmonary disease (COPD), and is an independent risk factor for increased mortality, increased emphysema, and more severe airflow obstruction. The variable development of cachexia among patients with COPD suggests a role for genetic susceptibility. The objective of the present study was to determine genetic susceptibility loci involved in the development of low BMI and FFMI in subjects with COPD. A genome-wide association study (GWAS) of BMI was conducted in three independent cohorts of European descent with Global Initiative for Chronic Obstructive Lung Disease stage II or higher COPD: Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-Points (ECLIPSE; n = 1,734); Norway-Bergen cohort (n = 851); and a subset of subjects from the National Emphysema Treatment Trial (NETT; n = 365). A genome-wide association of FFMI was conducted in two of the cohorts (ECLIPSE and Norway). In the combined analyses, a significant association was found between rs8050136, located in the first intron of the fat mass and obesity-associated (FTO) gene, and BMI (P = 4.97 × 10(-7)) and FFMI (P = 1.19 × 10(-7)). We replicated the association in a fourth, independent cohort consisting of 502 subjects with COPD from COPDGene (P = 6 × 10(-3)). Within the largest contributing cohort of our analysis, lung function, as assessed by forced expiratory volume at 1 second, varied significantly by FTO genotype. Our analysis suggests a potential role for the FTO locus in the determination of anthropomorphic measures associated with COPD.
Authors: Emily S. Wan, Michael H. Cho, Nadia Boutaoui, Barbara J. Klanderman, Jody S. Sylvia, John P. Ziniti, Sungho Won, Christoph Lange, Sreekumar G. Pillai, Wayne H. Anderson, Xiangyang Kong, David A. Lomas, Per S. Bakke, Amund Gulsvik, Elizabeth A. Regan, James R. Murphy, Barry J. Make, James D. Crapo, Emiel F. Wouters, Bartolome R. Celli, Edwin K. Silverman, Dawn L. DeMeo
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Alpha-1 Foundation, Pfizer, AstraZeneca, GlaxoSmithKline, Wellcome Trust, National Jewish Health, Amicus Therapeutics, British Lung Foundation, Astellas Pharma, National Institutes of Health, Agency for Healthcare Research and Quality, Centers for Medicare and Medicaid Services, Medical Research Council, National Heart, Lung, and Blood Institute
Awards: CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G1207659464, G1220799682, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, G1439225947, G1576662596, G1615620936, CLINICAL CENTER FOR LVRS, G1735610881, CLNICAL CENTER FOR LVRS, CLNICAL CENTER FOR LVRS, G182694510, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G229018656, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2412257637, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2599011918, G278468722, G3110798224, G3805264881, G4153249725, Genetic Determinants of COPD in Diverse Ethnic Groups, G4255341634, Fine Mapping of COPD Susceptibility Genes, G48533833, G5258357286, G556935766, (2 of 2) Genetic Epidemiology of COPD, G6160285194, G6315211796, CLNICAL CENTER FOR THE LVRS, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, CLINICAL CENTER FOR LVRS, (1 of 2) Genetic Epidemiology of COPD, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G778147052, G794209665, G7949433598, G8354759825, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G9000091268, G9000228787, SYSTEMS APPROACHES TO THE EPIDEMIOLOGY, GENETICS AND GENOMICS OF LUNG DISEASES, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY
OpenAlex ID: W2024612440