GENETIC-ANALYSIS OF ATOPY AND ASTHMA AS QUANTITATIVE TRAITS AND ORDERED POLYCHOTOMIES

Traits related to atopy and asthma were defined in a random cohort of 131 families with three or more children. Correlation analysis provide s no evidence of imprinting, maternal effect, or a major role of envir onment shared by sibs. Commingling analysis favours more than one dist ribution, the upper one being common for asthma and very common for at opy. Segregation analysis of rank-transformed variables provides only equivocal evidence of major genes against a polygenic background but s uggests that such genes (if present) are individually common and not o f large effect. Segregation analysis under a two-locus model gives con sistent results with minimal distributional assumptions. To enter comb ined segregation analysis we favour a restricted model in which the ma jor locus is additive on the liability scale and the pseudopolygenic m odifier locus accounts for at least half the genetic variance. Total I gE and bronchial reactivity are proposed for meta-analysis of atopy an d asthma respectively. Genetic analysis of complex inheritance is disc ussed and it is shown that allelic association with random loci is not a feasible approach.