Modeling age of onset and residual familial correlations for the linkage analysis of bipolar disorder.

We applied regressive modeling to the data described by Stine et al. [1995] and further explored the possible linkage of bipolar disorder to marker D18S41 on chromosome 18. We performed analyses to determine age-dependent penetrance functions that best fit the data and that allow for residual familial correlations. Specifically, we introduce here a simple method to allow for a sibling correlations. that is not due to segregation at the linked locus, and then extend the results of Stine et al. [1995] by using the best fitting "regressive" model of this kind as input into a lod score linkage analysis. Although a formal segregation analysis was not attempted, a surprising finding was that, except for doubtful linkage to D18S41, there is little evidence for genetic transmission of bipolar disorder in these families.