A bivariate Haseman-Elston method and application to the analysis of asthma-related phenotypes on chromosome 5q.

We propose a bivariate combination of different Haseman-Elston (HE) methods for model free linkage analysis of quantitative traits. Adjustments for correlations of phenotypes and sibship sizes > 2 are performed using generalized estimating equations (GEE). All calculations are carried out with freely available software packages. We illustrate the application of standard HE methods, the unified HE method, and our novel approach to asthma-associated quantitative traits from the COAG-Perth data set [Palmer et al., 1998, Am J Respir Crit Care Med 158:1825-30]. Our multipoint analyses provide evidence for linkage between log IgE levels adjusted for age, gender and antigen-specific IgE titers. Our results are consistent with previous findings that suggest the existence of loci regulating asthma-associated quantitative traits in the 5q31-33 chromosomal region. Simulation studies are required to compare the power of our novel bivariate HE with other HE approaches and the variance component method.