EXPLORING LINKAGE OF CHROMOSOME-18 MARKERS AND BIPOLAR DISEASE

The linkage reports of bipolar disease and chromosome 18 markers are c ontroversial. We used the GAW10 data sets to further explore several o bservations: 1) a possible parent-of-origin effect with only 'paternal ' pedigrees showing linkage; 2) the preponderance of women affected wi th bipolar disease, and 3) the possible existence of phenocopies in th e bipolar data sets. We performed linkage analysis allowing for indepe ndent male/female recombination fractions. Our hypothesis was that if there is linkage only in 'paternal' pedigrees, then the lod score woul d maximize at low male and high female recombination fractions. We did not find such an effect in the combined data set. There was no consis tent effect on the difference of male and female recombination fractio ns, suggesting that an effect is not detectable in this data set with this method. In addition, there is interesting evidence for a recessiv ely inherited, highly penetrant gene in a subset of families. Allowing for higher penetrances for bipolar disease in women than in men had n o effect on the lod scores. There was also not much difference in the lod scores calculated under the assumption of a phenocopy rate versus no phenocopies. From simulation studies, we would have expected some e ffect if there were linkage and phenocopies were present. (C) 1997 Wil ey-Liss, Inc.