Familial aggregation in chronic obstructive pulmonary disease: Use of the loglinear model to analyze intermediate environmental and genetic risk factors

Muin J. Khoury, Terri H. Beaty, Melvyn S. Tockman, Steven G. Self, Bernice H. Cohen

Research output: Contribution to journalArticle


To examine the contribution of environmental and genetic risk factors to familial aggregation in chronic obstructive pulmonary disease (COPD), 325 first‐degree (ld) relatives and 56 spouses of 150 COPD patients were compared with 222 ld relatives and 49 spouses of 107 nonpulmonary patient controls for the prevalence of two clinical outcomes: 1) airways obstruction (AO; 1‐sec forced expiratory volume < 68% of forced vital capacity) and 2) chronic bronchitis (CB; cough and sputum for 3+ months per year for 2+ years). The loglinear model was used to study direct and indirect (ie, those mediated by other risk factors) components of familial aggregation. Three risk factors were found to be independently associated with CB and/or AO: α1‐antitrypsin deficiency (PiZ allele), personal cigarette smoking, and parental cigarette smoking. Because ld relatives of COPD patients were more likely to have a PiZ allele, be heavy smokers (1 + packs per day), and be exposed to parental smoking than ld relatives of controls, these three factors also constitute indirect components of familial aggregation. However, after controlling for the three factors, ld relatives of COPD patients were more likely to have AO and CB than ld relatives of controls (direct component). This direct component might have a genetic basis, because no such association was found when spouses instead of ld relatives were compared. Thus, both shared environmental factors (personal and passive smoking) and shared genetic factors (α1‐antitrypsin and a possible direct genetic component) contribute to familial aggregation in COPD. The loglinear model provides a useful tool for analyzing familial aggregation in diseases of multifactorial etiology.

Original languageEnglish (US)
Pages (from-to)155-166
Number of pages12
JournalGenetic epidemiology
Issue number2
StatePublished - Jan 1 1985


ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

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