The role of heritability in mapping expression quantitative trait loci

Gene expression, as a heritable complex trait, has recently been used in many genome-wide linkage studies. The estimated overall heritability of each trait may be considered as evidence of a genetic contribution to the total phenotypic variation, which implies the possibility of mapping genome regions responsible for the gene expression variation via linkage analysis. However, heritability has been found to be an inconsistent predictor of significant linkage signals. To investigate this issue in human studies, we performed genome-wide linkage analysis on the 3554 gene expression traits of 194 Centre d'Etude du Polymorphisme Humain individuals provided by Genetic Analysis Workshop 15. Out of the 422 expression traits with significant linkage signals identified (LOD > 5.3), 89 traits have low estimated heritability (h2 < 10%), among which 23 traits have an estimated heritability equal to 0. The linkage analysis on individual pedigree shows that the overall LOD scores may result from a few pedigrees with strong linkage signals. Screening gene expressions before linkage analysis using a relatively low heritability (h2 < 20%) may result in a loss of significant linkage signals, especially for trans-acting expression quantitative trait loci (49%).