Chromosome 13q13-q14 locus overlaps mood and psychotic disorders: The relevance for redefining phenotype

The nosology of major psychoses is challenged by the findings that schizophrenia (SZ) and bipolar disorder (BP) share several neurobiological, neuropsychological and clinical phenotypic characteristics. Moreover, several vulnerability loci or genes may be common to the two DSM disorders. We previously reported, in a sample of 21 kindreds (sample 1), a genome-wide suggestive linkage in 13q13-q14 with a common locus (CL) phenotype that crossed the diagnostic boundaries by combining SZ, BP and schizoaffective disorders. Our objectives were to test phenotype specificity in a separate sample (sample 2) of 27 kindreds from Eastern Quebec and to also analyze the combined sample of 48 kindreds (1274 family members). We performed nonparametric and parametric analyses and tested as phenotypes: SZ alone, BP alone, and a CL phenotype. We replicated in sample 2 our initial finding with CL with a maximum NPL_pair score of 3.36 at D13S1272 (44Mb), only 2.1Mb telomeric to our previous maximum result. In the combined sample, the peak with CL was at marker D13S1297 (42.1Mb) with a NPL_pair score reaching 5.21, exceeding that obtained in each sample and indicating consistency across the two samples. Our data suggest a susceptibility locus in 13q13-q14 that is shared by schizophrenia and mood disorder. That locus would be additional to another well documented and more distal 13q locus where the G72/G30 gene is mapped.