Simulation studies of segregation analysis: application to two-locus models

We tested the power of a segregation analysis method (first proposed by Elandt-Johnson) to distinguish between single-locus and two-locus models, with and without environmentally caused reduced penetrance. We also looked at the effect of ascertainment probability on the analysis and at the proband-conditioned ascertainment correction proposed by Cannings and Thompson. We found that: (1) the segregation analysis has sufficient power to distinguish between the fully-penetrant double-recessive (RR) model and the fully-penetrant single-locus dominant and recessive models; (2) the method can also distinguish fairly well between the dominant-recessive (DR) and RR models, even when one does not take into account the population prevalence; (3) the method has much less power to distinguish between the fully-penetrant RR model and the single-locus models with reduced penetrance; (4) when environmental penetrance is taken account of in the analysis, the power of the method to distinguish between the one- and two-locus models improved substantially; (5) the estimates of ascertainment probability, pi, were robust, regardless of the model under which the data were generated; and (6) the Cannings-Thompson approach to ascertainment correction worked well only when the pi used to generate the data was less than .1.