Familial correlation and segregation analysis of forced expiratory volume in one second (FEV₁), with and without smoking adjustments, in a Tucson population

Abstract

BACKGROUND: Previous researchers have found significant familial aggregation but no evidence of Mendelian inheritance of forced expiratory volume in one second (FEV₁) in general population studies. However, the influence of cigarette smoking on familial aggregation of FEV₁ has been difficult to assess in these studies. OBJECTIVES: The main objective of our study was to attempt to discern the effects of smoking on familial correlation and segregation models of FEV₁. SUBJECTS AND METHODS: In a randomly selected sample of white, non-Mexican American families in Tucson, Arizona, we performed two separate familial correlation and segregation analyses of FEV₁, one adjusted for cigarette smoking and one unadjusted for smoking. In both, initial survey measures of FEV₁ for 1329 females and 1291 males in 746 families were standardized for gender, age, height and height-squared using piecewise linear regression models. In the smoking-adjusted model, total number of pack-years smoked, current and ex-smoking status, and the interaction between total pack-years and current smoking status were also included. RESULTS: FEV₁ was significantly correlated among sibling pairs and parent-offspring pairs (both p < 0.001), regardless of smoking adjustment, but sibling correlation was significantly higher than parent-offspring correlation (p < 0.05), suggesting additional effects beyond common parentage. Spousal correlations were not significant even when both spouses smoked. We found no evidence of major gene segregation of FEV₁, with or without smoking adjustment, and all of the segregation models were significantly different from the unrestricted model. CONCLUSIONS: The best-fitting model was an environmental model with three distinct distributions of FEV₁ and significant residual familial effects. A significant familial component suggests the presence of polygenic factors and/or effects due to a shared environment (multifactorial). That familial correlations of smoking-adjusted and smoking-unadjusted residuals were not appreciably different suggests that current smoking status and number of packyears smoked do not account for the observed familial aggregation of FEV₁.