Linkage analysis under "random" and "genetic" reduced penetrance.

We examined whether the results of linkage analysis are affected by the reasons for so-called "reduced penetrance". We simulated linkage data with random reduced penetrance and contrasted that with data that were simulated under inheritance controlled by two loci interacting epistatically. For the two-locus disease models, one of those loci was linked to the marker. All data, irrespective of how the data were simulated, were analyzed under the assumption of a single-locus genetic model with random reduced penetrance. We found that there appears to be little bias in the results of linkage analysis whether the "reduced penetrance" was caused by random (usually interpreted as environmental) factors or by strictly genetic factors. We also illustrate that when the trait or disease is influenced by more than one locus, the inheritance of the trait at the linked locus is the important consideration, not the inheritance of the trait per se.