Linkage analysis of asthma and atopy including models with genomic imprinting

Asthma and atopy are two closely related, common complex traits in which a number of genetic and environmental factors are suspected to play a role. W e have performed parametric and nonparametric multi-marker linkage analysis for the Busselton data set, which is part of problem I of Genetic Analysis Workshop 12. In particular, we have focused on the dichotomous trait atopy , as well as on dichotomized versions of the quantitative traits RASTI and log, slope. The lod score analysis with adequate modeling of a parent-of-or igin effect, by use of the program GENEHUNTER-IMPRINTING, was of special in terest. The most prominent findings are a multipoint mod score of 3.12 at D 13S153 for RASTI, and a multipoint mod score of 4.32 at the same locus for atopy, both with four-penetrance imprinting models that point to a gene sub ject to maternal imprinting. In addition, there are marked differences betw een imprinting and non-imprinting mod scores. These results corroborate ear lier findings of linkage between atopy and D13S153, but add the aspect of p aternal gene expression. Furthermore, suggestive evidence for linkage to at opy is found near D6S291, D7S530, and D14S74. The best-fitting models for c hromosome 6 and 14 may suggest that genomic imprinting takes place at these two loci as well. (C) 2001 Wiley-Liss, Inc.