title: Genetic analysis of atopy and asthma as quantitative traits and ordered polychotomies.
abstract: Traits related to atopy and asthma were defined in a random cohort of 131 families with three or more children. Correlation analysis provides no evidence of imprinting, maternal effect, or a major role of environment shared by sibs. Commingling analysis favours more than one distribution, the upper one being common for asthma and very common for atopy. Segregation analysis of rank-transformed variables provides only equivocal evidence of major genes against a polygenic background but suggests that such genes (if present) are individually common and not of large effect. Segregation analysis under a two-locus model gives consistent results with minimal distributional assumptions. To enter combined segregation analysis we favour a restricted model in which the major locus is additive on the liability scale and the pseudopolygenic modifier locus accounts for at least half the genetic variance. Total IgE and bronchial reactivity are proposed for meta-analysis of atopy and asthma respectively. Genetic analysis of complex inheritance is discussed and it is shown that allelic association with random loci is not a feasible approach.
authors.affiliation: Human Genetics Centre, University of Southampton, Princess Anne Hospital.
authors.forename: S
authors.initials: S
authors.lastname: Lawrence
authors.forename: R
authors.initials: R
authors.lastname: Beasley
authors.forename: I
authors.initials: I
authors.lastname: Doull
authors.forename: B
authors.initials: B
authors.lastname: Begishvili
authors.forename: F
authors.initials: F
authors.lastname: Lampe
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: N E
authors.initials: NE
authors.lastname: Morton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics*; D016535:Bronchial Hyperreactivity; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D007073:Immunoglobulin E / Q000235:genetics*; D008222:Lymphokines; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D029584:Prostatic Secretory Proteins
chemical_list: D008222:Lymphokines; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors; D007073:Immunoglobulin E