Differences in familial segregation of FEV1 between asthmatic and nonasthmatic families. Role of a maternal component.

Studies have demonstrated familial aggregation of lung function. This study employed segregation analysis to investigate the mode of inheritance of FEV1 using regressive models for continuous traits. The study population comprised 309 families (1,163 individuals) enrolled in the Tucson Children's Respiratory Study who had both parents and at least one child with FEV1 data. Results showed significant genetic heterogeneity among the 87 families (328 individuals) with at least one member with asthma and the 222 families (835 individuals) with no asthmatic members. In families with no asthmatic members, all statistical models were rejected, indicating the absence of a major gene controlling lung function. However, a significant familial component indicated a strong polygenic/multifactorial mode of inheritance. In families with asthmatic member(s), results suggested polygenic/multifactorial inheritance with weak evidence for a Mendelian component expressed in a recessive fashion. However, while both father-offspring and mother-offspring correlations were statistically significant in families with no asthmatic members, only the mother-offspring correlation was significant in families with asthmatic members. The data suggest that lung function is inherited as a polygenic/multifactorial trait, but in asthmatic families a major element of intergenerational correlation is associated with a maternal influence, which may be genetically or environmentally mediated.