Effects of genotype-by-sex interaction on quantitative trait linkage analysis

Genotype-by-sex (G x S) interaction refers to the interaction of autosomal genes with male or female physiological "environments." G x S interaction has been demonstrated in quantitative genetic analysis of a variety of traits including serum lipid concentrations and anthropometrics, and the importance of considering sex-specific major gene effects in segregation analyses also has been demonstrated. The goal of this study was to examine the effects of G x S interaction on the power to detect linkage. Trait Q3 in GAW10 Problem 2 was analyzed because it was modeled to have G x S interaction at the major gene locus MG3. All 200 nuclear family and 200 extended pedigree replicates were first screened for the presence of G x S interaction in Q3 using a quantitative genetic method. More than half of both the nuclear family and extended pedigree replicates evidenced significant G x S interaction. Variance components linkage analysis was then performed using all markers on GAW10 chromosome 4 in all 200 nuclear family and 200 extended pedigree replicates. A peak lod score of 1.92 at the correct chromosomal location was obtained using the extended pedigree data and incorporating G x S interaction effects. Not incorporating G x S interaction lowered the peak lod score from the analyses of the extended pedigrees to 1.53. Incorporation of G x S interaction effects also increased the power to detect linkage in the nuclear family replicates, although the nuclear families had considerably less power than the extended pedigrees to detect linkage, whether or not G x S interaction was modeled. Incorporation of G x S interaction effects can increase the power to detect linkage, even when the G x S interaction effects are modest.