Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene

In the course of a systematic genomic survey, 22 manic-depressive (bipolar) families were examined for linkage to 11 chromosome 18 pericentromeric marker loci, under dominant and recessive models. Overall logarithm of odds score analysis for the pedigree series was not significant under either model, but several families yielded logarithm of odds scores consistent with linkage under dominant or recessive models. Affected sibling pair analysis of these data yielded evidence for linkage (P < 0.001) at D18S21. Affected pedigree member analysis also suggests linkage, with multilocus results for five loci giving P < 0.0001 and P = 0.0007 for weighting functions f(p) = 1 and 1/square root p, respectively, where p is the allele frequency. These results imply a susceptibility gene in the pericentromeric region of chromosome 18, with a complex mode of inheritance. Two plausible candidate genes, a corticotropin receptor and the alpha subunit of a GTP binding protein, have been localized to this region.