Adaptations of linkage and association methods for the study of asthma, a complex trait

Early studies that found significant linkage between markers on 5q and asthma and IgE have not been reproduced. In an attempt to improve the power of these studies we performed a variance components linkage analysis and transmission-disequilibrium tests (TDT) with haplotypes using markers on 5q, using the Southampton and Perth data sets supplied by GAW. The linkage analysis with covariates revealed a maximum lod of 1.57 in the Perth families. The addition of age and RAST significantly improved the fit of the null models but did not improve the lod scores. The TDT tests showed a marginally significant association with D5S393 and D5S399 and with three markers together (IL9, IL4, D5S393). We conclude that further studies are needed to delineate the environmental contribution to this disease so that the genetic factors can be more easily identified. In addition, haplotype analysis may help to identify specific genetic effects.