MODELING THE PHENOTYPE IN PARAMETRIC LINKAGE ANALYSIS OF BIPOLAR DISORDER

The definition of phenotype is a major problem in genetic studies of p sychiatric disorders. Most linkage studies in bipolar disorder have de fined the phenotype as a dichotomous trait and have usually employed d ifferent hierarchical classifications in order to overcome uncertainty resulting from phenotypic variability. In this study we explored the advantages of maximizing the evidence for linkage over different pheno typic definitions when conducting parametric linkage analysis of a com plex trait. The GAW10 Problem 1 was used, focusing on chromosome 18 da ta sets. Three major phenotypic models were analyzed: quasi-quantitati ve, liability-based and affection-status models. Overall, no single ph enotypic model performed consistently better than the others (i.e., lo d scores greater than 1.0). Each model yielded higher lod scores than the others in particular instances, suggesting that it might be useful in exploratory data analysis, where the phenotype is variable, to max imize evidence for linkage over different phenotypic models. (C) 1997 Wiley-Liss, Inc.