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Asthma now affects one child in seven in the United Kingdom. Most cases (95%) of childhood asthma are associated with atopy, the immunoglobulin E (IgE)-mediated familial syndrome of allergic asthma, eczema and rhinitis. Segregation analysis has consistently suggested the presence of major genes influencing atopy and IgE levels, with the expectation that these genes may be identified by positional cloning or the examination of candidate genes. Here we report the results of a genome-wide search for linkage to one qualitative and four quantitative traits associated with allergic (atopic) asthma. We have identified six potential linkages (P<0.001), five of which are to quantitative traits. Monte Carlo simulations show that 1.6 false-positive linkages at this level of significance would be expected from the data. One linkage, to chromosome 11q13, has been established previously. Three of the new loci show evidence of linkage to a second panel of families, in which maternal effects and pleiotropy of linked phenotypes are seen. The results demonstrate the extent and the complexity of the genetic predisposition to asthma.

Atopy is a common and genetically heterogeneous syndrome predisposing to allergic asthma and rhinitis. A locus linked to the atopy phenotype has been shown to be present on chromosome 11q12-13. Linkage has only been seen in maternally derived alleles. We have constructed a genetic linkage map of the region, using 15 markers to span approximately 27 cM, and integrate previously published maps. Under a model of maternal inheritance, the atopy locus is placed within a 7-cM interval between D11S480 and D11S451. The interval contains the important candidate gene FCERIB.