title: Heritability of chronic obstructive pulmonary disease and related phenotypes in smokers.
abstract: BACKGROUND
  Previous studies of chronic obstructive pulmonary disease (COPD) have suggested that genetic factors play an important role in the development of disease. However, single-nucleotide polymorphisms that are associated with COPD in genome-wide association studies have been shown to account for only a small percentage of the genetic variance in phenotypes of COPD, such as spirometry and imaging variables. These phenotypes are highly predictive of disease, and family studies have shown that spirometric phenotypes are heritable.
  
  
  OBJECTIVE
  To assess the heritability and coheritability of four major COPD-related phenotypes (measurements of FEV1, FEV1/FVC, percent emphysema, and percent gas trapping), and COPD affection status in smokers of non-Hispanic white and African American descent using a population design.
  
  
  METHODS
  Single-nucleotide polymorphisms from genome-wide association studies chips were used to calculate the relatedness of pairs of individuals and a mixed model was adopted to estimate genetic variance and covariance.
  
  
  RESULTS
  In the non-Hispanic whites, estimated heritabilities of FEV1 and FEV1/FVC were both about 37%, consistent with estimates in the literature from family-based studies. For chest computed tomography scan phenotypes, estimated heritabilities were both close to 25%. Heritability of COPD affection status was estimated as 37.7% in both populations.
  
  
  CONCLUSIONS
  This study suggests that a large portion of the genetic risk of COPD is yet to be discovered and gives rationale for additional genetic studies of COPD. The estimates of coheritability (genetic covariance) for pairs of the phenotypes suggest considerable overlap of causal genetic loci.
authors: 1 Biostatistics Department, Harvard School of Public Health, Boston, Massachusetts.
authors: Jin J
authors: JJ
authors: Zhou
authors: Michael H
authors: MH
authors: Cho
authors: Peter J
authors: PJ
authors: Castaldi
authors: Craig P
authors: CP
authors: Hersh
authors: Edwin K
authors: EK
authors: Silverman
authors: Nan M
authors: NM
authors: Laird
mesh_terms: D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D044469:Racial Groups / Q000235:genetics; D012907:Smoking / Q000009:adverse effects* / Q000503:physiopathology; D014797:Vital Capacity / Q000235:genetics
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