Likelihood formulation of parent-of-origin effects on segregation analysis, including ascertainment

We developed a likelihood-based method for testing for parent-of-origin eff ect in complex diseases. The likelihood formulations model parent-of-origin effect and allow for incorporation of ascertainment, as well as differenti al male and female ascertainment probabilities. The results based on simula ted data indicated that the estimates of parental effect (either maternal o r paternal) were biased when ascertainment was ignored or when the wrong as certainment model was used. The exception was single ascertainment, in whic h we proved that ignoring ascertainment does not bias the estimation of par ental effect, in a simple parent-of-origin model. These results underscore the importance of considering ascertainment models when testing for parent- of-origin effect in complex diseases.