CHROMOSOME-18 DNA MARKERS AND MANIC-DEPRESSIVE ILLNESS - EVIDENCE FORA SUSCEPTIBILITY GENE

In the course of a systematic genomic survey, 22 manic-depressive (bip olar) families were examined for linkage to 11 chromosome 18 pericentr omeric marker loci, under dominant and recessive models. Overall logar ithm of odds score analysis for the pedigree series was not significan t under either model, but several families yielded logarithm of odds s cores consistent with linkage under dominant or recessive models. Affe cted 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/root p, respectively , where p is the allele frequency. These results imply a susceptibilit y gene in the pericentromeric region of chromosome 18, with a complex mode of inheritance. Two plausible candidate genes, a corticotropin re ceptor and the alpha subunit of a GTP binding protein, have been local ized to this region.