Note on linkage analysis when the mode of transmission is unknown

A major difficulty in a linkage analysis arises from the necessity of specifying the mode of inheritance prior to analysis. For a complex disease, such as those encountered in psychiatric illnesses, the mode of inheritance is generally not known in advance. Consequently, some estimation procedure is often combined with linkage analysis to circumvent this. We discuss several precautions that should be taken when using traditional statistical testing methods: correction of the likelihood for the method of sampling families and the computation of the lod score. We analyze simulated data with pedigrees selected under a sampling scheme approximating single ascertainment. In this situation, the severity of the above problems is attenuated.