Power to localize the major gene for disease liability is increased after accounting for the effects of related quantitative phenotypes.

We used the simulated general population data for Genetic Analysis Workshop 12 to test whether power to localize the major gene for liability to disease is increased after accounting for the effects of correlated quantitative phenotypes. We performed the multipoint variance-component linkage analyses for the discrete trait twice: first analysis with age, sex, and EF1 as covariates, and the second analysis with age, sex, EF1, and Q1-Q5 as covariates. Major locus heritability (h2q) (0.80 +/- 0.06) and lod score (6.4) averaged over the number of replicates used are significantly higher in the second analysis compared with the first analysis (h2q = 0.39 +/- 0.12, lod = 2.6). Thus, in the present analysis, power to detect linkage and localize the genes for liability to disease appears to be increased after accounting for the effects of five quantitative traits that are correlated with the liability.