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

Background: Previous researchers have found significant familial aggregatio n but no evidence of Mendelian inheritance of forced expiratory volume in o ne second (FEV1) in general population studies. However, the influence of c igarette smoking on familial aggregation of FEV1 has been difficult to asse ss in these studies. Objectives: The main objective of our study was to attempt to discern the e ffects of smoking on familial correlation and segregation models of FEV1. Subjects and methods: In a randomly selected sample of white, non-Mexican A merican families in Tucson, Arizona, we performed two separate familial cor relation and segregation analyses of FEV1, one adjusted for cigarette smoki ng and one unadjusted for smoking. In both, initial survey measures of FEV1 for 1329 females and 1291 males in 746 families were standardized for gend er, 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 cu rrent smoking status were also included. Results: FEV1 was significantly correlated among sibling pairs and parent-o ffspring pairs (both p < 0.001), regardless of smoking adjustment, but sibl ing correlation was significantly higher than parent-offspring correlation (p < 0.05) suggesting additional effects beyond common parentage. Spousal c orrelations were not significant even when both spouses smoked. We found no evidence of major gene segregation of FEV1, with or without smoking adjust ment, and all of the segregation models were significantly different from t he unrestricted model. Conclusions: The best-fitting model was an environmental model with three d istinct distributions of FEV1 and significant residual familial effects. A significant familial component suggests the presence of polygenic factors a nd/or effects due to a shared environment (multifactorial). That familial c orrelations of smoking-adjusted and smoking-unadjusted residuals were not a ppreciably different suggests that current smoking status and number of pac k-years smoked do not account for the observed familial aggregation of FEV1 .