Genetic linkage and association analysis of COPD-related traits on chromosome 8p

COPD. 2006 Dec;3(4):189-94. doi: 10.1080/15412550601009321.


Genome-wide linkage analysis in the Boston Early-Onset Chronic Obstructive Pulmonary Disease (COPD) Study has demonstrated significant evidence of linkage to chromosome 8p for forced expiratory volume in 1 second, an important COPD-related phenotype. In this study, we sought to fine map the linkage peak and to test variants in two candidate genes for association with COPD and related traits. In a variance component linkage analysis on chromosome 8, including seven additional short tandem repeat markers, the logarithm of the odds of linkage score was reduced from 3.30 to 1.80 (at 1 cM). Five single nucleotide polymorphisms (SNPs) in Defensin Beta-1 (DEFB1) were genotyped in the Boston Early-Onset COPD Study families; none was significantly associated. Four SNPs and an insertion-deletion polymorphism in Macrophage Scavenger Receptor-1 (MSR1) were also genotyped in the family-based study. A coding variant (Pro275Ala) was marginally associated with two qualitative airflow obstruction traits (p < or = 0.02). This SNP showed a trend toward association in a case-control study comparing participants in the National Emphysema Treatment Trial to smoker controls (p = 0.07). Despite the reduced support for linkage upon further analysis, it remains possible that chromosome 8p contains a gene that influences COPD susceptibility. There is marginal, though not convincing, evidence for association with MSR1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Chromosomes, Human, Pair 8 / genetics*
  • DNA / genetics*
  • Female
  • Forced Expiratory Volume / genetics
  • Gene Frequency
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quantitative Trait, Heritable*
  • Retrospective Studies
  • Scavenger Receptors, Class A / genetics*
  • beta-Defensins / genetics*


  • DEFB1 protein, human
  • MSR1 protein, human
  • Scavenger Receptors, Class A
  • beta-Defensins
  • DNA