Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/122524
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Type: Journal article
Title: Genomewide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary disease
Author: Silverman, E.
Palmer, L.
Mosley, J.
Barth, M.
Senter, J.
Brown, A.
Drazen, J.
Kwiatkowski, D.
Chapman, H.
Campbell, E.
Province, M.
Rao, D.
Reilly, J.
Ginns, L.
Speizer, F.
Weiss, S.
Citation: American Journal of Human Genetics, 2002; 70(5):1229-1239
Publisher: Elsevier
Issue Date: 2002
ISSN: 0002-9297
1537-6605
Statement of
Responsibility: 
Edwin K. Silverman, Lyle J. Palmer, Jonathan D. Mosley, Matthew Barth, Jody M. Senter, Alison Brown, Jeffrey M. Drazen, David J. Kwiatkowski, Harold A. Chapman, Edward J. Campbell, Michael A. Province, D. C. Rao, John J. Reilly, Leo C. Ginns, Frank E. Speizer, and Scott T. Weiss
Abstract: Chronic obstructive pulmonary disease (COPD) is a common, complex disease associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction; airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC). To identify genetic determinants of quantitative spirometric phenotypes, an autosomal 10-cM genomewide scan of short tandem repeat (STR) polymorphic markers was performed in 72 pedigrees (585 individuals) ascertained through probands with severe early-onset COPD. Multipoint variance-component linkage analysis (using SOLAR) was performed for quantitative phenotypes, including FEV(1), FVC, and FEV(1)/FVC. In the initial genomewide scan, significant evidence for linkage to FEV(1)/FVC was demonstrated on chromosome 2q (LOD score 4.12 at 222 cM). Suggestive evidence was found for linkage to FEV(1)/FVC on chromosomes 1 (LOD score 1.92 at 120 cM) and 17 (LOD score 2.03 at 67 cM) and to FVC on chromosome 1 (LOD score 2.05 at 13 cM). The highest LOD score for FEV(1) in the initial genomewide scan was 1.53, on chromosome 12, at 36 cM. After inclusion of 12 additional STR markers on chromosome 12p, which had been previously genotyped in this population, suggestive evidence for linkage of FEV(1) (LOD score 2.43 at 37 cM) to this region was demonstrated. These observations provide both significant evidence for an early-onset COPD-susceptibility locus on chromosome 2 and suggestive evidence for linkage of spirometry-related phenotypes to several other genomic regions. The significant linkage of FEV(1)/FVC to chromosome 2q could reflect one or more genes influencing the development of airflow obstruction or dysanapsis.
Keywords: Chromosomes, Human
Chromosomes, Human, Pair 12
Pulmonary Disease, Chronic Obstructive
Genetic Predisposition to Disease
Respiratory Function Tests
Forced Expiratory Volume
Spirometry
Chromosome Mapping
Pedigree
Age of Onset
Tandem Repeat Sequences
Lod Score
Phenotype
Polymorphism, Genetic
Genome, Human
Rights: Copyright © 2002 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
DOI: 10.1086/340316
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