Detailed analysis of cytokine responses in this very young age group have the potential to uncover subtle relationships between in vivo and in vitro allergen reactivity which may be less clear in adults, in whom T-cell response patterns are modified via chronic stimulation. The present findings which suggest potentially important roles for IL-9 and IL-10 in the early phase of allergic disease, may be one such example.

The common complex diseases such as asthma are an important focus of genetic research, and studies based on large numbers of simple pedigrees ascertained from population‐based sampling frames are becoming commonplace. Many of the genetic and environmental factors causing these diseases are unknown and there is often a strong residual covariance between relatives even after all known determinants are taken into account. This must be modelled correctly whether scientific interest is focused on fixed effects, as in an association analysis, or on the covariances themselves. Analysis is straightforward for multivariate Normal phenotypes, but difficulties arise with other types of trait. Generalized linear mixed models (GLMMs) offer a potentially unifying approach to analysis for many classes of phenotype including multivariate Normal traits, binary traits, and censored survival times. Markov Chain Monte Carlo methods, including Gibbs sampling, provide a convenient framework within which such models may be fitted. In this paper, Bayesian inference Using Gibbs Sampling (a generic Gibbs sampler; BUGS) is used to fit GLMMs for multivariate Normal and binary phenotypes in nuclear families. BUGS is easy to use and readily available. We motivate a suitable model structure for Normal phenotypes and show how the model extends to binary traits. We discuss parameter interpretation and statistical inference and show how to circumvent a number of important theoretical and practical problems that we encountered. Using simulated data we show that model parameters seem consistent and appear unbiased in smaller data sets. We illustrate our methods using data from an ongoing cohort study. Genet. Epidemiol. 17:118–140, 1999. © 1999 Wiley‐Liss, Inc.

The polymorphism at position 27 was associated with decreased airway responsiveness in the study population and the polymorphism at position 16 was associated with increased wheeze during respiratory infection, but neither was associated with physician-diagnosed asthma or any of the other variables considered.

The diminishing incidence of parasitic infection in westernised societies has been suggested to result in an increased prevalance of asthma. Asthma is a polygenic disease and genome screens have shown that genes on chromosome 5q31-33 are strongly linked to the disease. The gene for the beta2-adrenoreceptor is located in this region and two polymorphisms have been identified that result in amino acid changes at positions 16 (ArgGly) and 27 (GlnGlu). To determine whether these polymorphisms influence asthma and parasitic infection, a genotype/phenotype study has been performed on a cohort of 126 children from Coche Island in Venezuela. There is a high incidence of asthma on the island and intestinal helminthiasis is endemic. Genotyping for both polymorphisms was carried out by using the polymerase chain reaction and allele-specific oligonucleotide hybridisation. Genotype frequencies in this cohort were consistent with other studies and both polymorphisms were in significant linkage disequilibrium. Individuals who were homozygous for Arg16 had significantly higher levels of specific IgE to Ascaris lumbricoides (P=0.002), significantly higher A. lumbricoides egg counts (P<0.001) and significantly larger wheal sizes following skin-prick testing with A. lumbricoides allergen (P=0.008). There was no association between either polymorphism and total serum IgE or asthma in this population. A combination of mast cell degranulation and the lung migratory phase of A. lumbricoides larvae may result in bronchoconstriction in infected individuals. These results suggest that the Gly 16 allele confers resistance to high levels of parasitic infection in this population. An alternative explanation for the association is that it may be the result of linkage disequilibrium with other genes in the chromosome 5q31-33 region.