A GENETIC-LINKAGE STUDY OF BIPOLAR DISORDER AND 13 MARKERS ON CHROMOSOME-11 INCLUDING THE D(2) DOPAMINE-RECEPTOR

Chromosome 11 is a region of great interest in the search for genes fo r bipolar disorder. Although an initial report of linkage to 11p15 was not replicated in numerous subsequent studies, the remainder of the c hromosome contains a variety of interesting candidate genes and region s. These include the D2 dopamine receptor and the site of a chromosoma l translocation that has been reported to be associated with bipolar d isorder. As part of a systematic survey of the genome for markers link ed to bipolar disorder, we have examined 13 markers on chromosome 11 i n three large Icelandic families and Amish pedigree 110. No clear evid ence of linkage was obtained. The highest lod score was found at D11S2 9 (lod = 1.63 at theta = 0.1), which is in the general region of the r eported translocation breakpoints. However, this lod is not statistica lly significant, and its meaning is further mitigated by strongly nega tive lods in two nearby flanking markers. Linkage to the D2 dopamine r eceptor locus was strongly excluded (lod = -4.02 at theta = 0.0). In t wo-point analyses, linkage to bipolar disorder could be excluded to ei ght of the 13 markers. Multipoint analyses, similarly, failed to revea l any evidence of linkage.