Genomic screening for genes predisposing to bipolar disease

Twenty-one multiplex bipolar (BP) families, consisting of 365 informative persons (of whom 153 have BPI, schizoaffective, BPII with major depression or recurrent unipolar diagnoses) were studied in a systematic screening of chromosomes 1, 10q, 11q, 13, 15 and 17 for linkage, using DNA markers. Simulation research has indicated that this pedigree series has greater than 50% power to detect linkage when only 25% of families are linked (1% recombination) to the marker. Two and three-point linkage analysis (using the diagnoses mentioned above as affected and an autosomal dominant disease mode1) did not reveal any evidence for linkage (total lod scores less than -2) under the hypothesis of homogeneity. Inspection of two-point lod scores by family did not reveal evidence for heterogeneity in nearly all cases. Heterogeneity analyses using the admixture test were conducted for a region of 11q13 (where inspection of 2-point analyses for individual families revealed several weakly positive lod scores) which yielded a maximum lod score of 1.5 when the fraction of linked families was estimated at 25%. These results indicate that a gene responsible for BP disease in a majority of the families studied is unlikely to originate within the chromosomal regions covered by the DNA markers used.