TEST OF XQ26.3-28 LINKAGE IN BIPOLAR AND UNIPOLAR AFFECTIVE-DISORDER IN FAMILIES SELECTED FOR ABSENCE OF MALE TO MALE TRANSMISSION

Background There have been several reports of linkage between genetic markers on the X chromosome at Xq26.3-28 and bipolar affective disorde r in family samples obtained from distinct ethnic and geographical ori gins. As part of a genome search in a series of 23 UK and Icelandic fa milies, specifically selected for their large size and power to resolv e the issue of linkage heterogeneity we have tested the hypothesis tha t there is a locus for a genetic subtype of bipolar affective disorder which is linked to this region. Method In families selected on the ba sis of absent male to male transmission for affective disorder, we per formed two-point and FASTMAP multipoint linkage analyses with markers spanning the region between the genetic loci DXSI02 and F8. Results We found negative lod scores for several models of affection status in f amilies selected under stringent and relaxed criteria for the absence of male to male transmission. Conclusions In the family sample we have obtained, our study provides no support for the presence of a locus i ncreasing genetic susceptibility to bipolar affective disorder in this region of the X chromosome. It is likely that our finding reflects he terogeneity of linkage For bipolar and genetically related unipolar di sorder that exists in specific ethnic populations. Alternatively the X -linked subtype of the disorder may have been present only in a Few of our smalt families resulting in loss of power to detect the Xq26.3-28 linked subtype.