Identifying a Deletion Affecting Total Lung Capacity Among Subjects in the COPDGene Study Cohort.
Chronic obstructive pulmonary disease (COPD) is a progressive disease with both environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified multiple genomic regions influencing risk of COPD. To thoroughly investigate the genetic etiology of COPD, however, it is also important to explore the role of copy number variants (CNVs) because the presence of structural variants can alter gene expression and can be causal for some diseases. Here, we investigated effects of polymorphic CNVs on quantitative measures of pulmonary function and chest computed tomography (CT) phenotypes among subjects enrolled in COPDGene, a multisite study. COPDGene subjects consist of roughly one-third African American (AA) and two-thirds non-Hispanic white adult smokers (with or without COPD). We estimated CNVs using PennCNV on 9,076 COPDGene subjects using Illumina's Omni-Express genome-wide marker array. We tested for association between polymorphic CNV components (defined as disjoint intervals of copy number regions) for several quantitative phenotypes associated with COPD within each racial group. Among the AAs, we identified a polymorphic CNV on chromosome 5q35.2 located between two genes (FAM153B and SIMK1, but also harboring several pseudo-genes) giving genome-wide significance in tests of association with total lung capacity (TLCCT ) as measured by chest CT scans. This is the first study of genome-wide association tests of polymorphic CNVs and TLCCT . Although the ARIC cohort did not have the phenotype of TLCCT , we found similar counts of CNV deletions and amplifications among AA and European subjects in this second cohort.
['Begum|Ferdouse|F|', 'Ruczinski|Ingo|I|', 'Li|Shengchao|S|', 'Silverman|Edwin K|EK|', 'Cho|Michael H|MH|', 'Lynch|David A|DA|', 'Curran-Everett|Douglas|D|', 'Crapo|James|J|', 'Scharpf|Robert B|RB|', 'Parker|Margaret M|MM|', 'Hetmanski|Jacqueline B|JB|', 'Beaty|Terri H|TH|']
D001741:African Americans D000368:Aged D015415:Biomarkers D002872:Chromosome Deletion D002895:Chromosomes, Human, Pair 5 D015331:Cohort Studies D056915:DNA Copy Number Variations D005260:Female D020022:Genetic Predisposition to Disease D055106:Genome-Wide Association Study D006801:Humans D008297:Male D008390:Markov Chains D008875:Middle Aged D029424:Pulmonary Disease, Chronic Obstructive D012907:Smoking D014109:Total Lung Capacity D044465:Whites
COPD genome-wide association study (GWAS) copy number variant (CNV) pulmonary function total lung capacity (TLCCT) lung hyperinflation