A genome-wide search for quantitative trait loci underlying asthma.
Daniels SE., Bhattacharrya S., James A., Leaves NI., Young A., Hill MR., Faux JA., Ryan GF., le Söuef PN., Lathrop GM., Musk AW., Cookson WO.
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.