Effects of Genotype-by-Sex Interaction on Quantitative Trait Linkage Analysis
Towne B, Siervogel RM, Blangero J
Department of Community Health, Wright State University School of Medicine,
Dayton, Ohio 45435, USA.
Genetic Epidemiology, 14(6):1035-1038 (1997)
Abstract
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.
Variance component linkage analysis