Estimating the additive genetic effect of the X chromosome.

We propose a method for efficient estimation of the additive genetic effect of the X chromosome with explicit modeling of eutherian-type dosage compensation. The theoretical derivation of the variance-components model for X-linked loci is reviewed in detail. We develop a model of dosage compensation that allows for both incomplete and heterogeneous lyonization, the existence of which is suggested by recent expression studies. Modeling this relationship, especially in the limit cases of complete or absent compensation, allows estimation of the X effect as a single parameter for ease of comparison to other sources of variance. We present simulation studies to estimate the power and computational efficiency of our proposed method.