X-linkage and genetic heterogeneity in bipolar-related major affective illness: reanalysis of linkage data

It has been suggested that an X-linked dominant allele operates in the genetic transmission of bipolar (manic-depressive) illness. Linkage studies with X-chromosome markers have remained inconclusive, showing both positive and negative results. Some of the ambiguity may be attributed to imprecise analytic methods and genetic heterogeneity. In this report, recently published pedigree series are reanalysed for linkage using a systematic method of pedigree analysis (Liped 3) with an accurate age-of-onset correction. Linkage heterogeneity is assessed through a two-recombination fraction heterogeneity test suggested by Smith (1963). The results are as follows: (1) Close linkage of bipolar illness to colourblindness (deutan and protan) and glucose-6-phosphate dehydrogenase deficiency appears to be present in some pedigrees, with estimated recombination fractions of theta = 0.05 and 0.00, respectively; (2) Linkage with the Xg blood group cannot be supported. These results are consistent with known linkages on the X chromosome.