Chromosome 1q12-q22 linkage results in eastern Québec families affected by schizophrenia

An impressive LOD score of 6.5 has recently been reported for schizophrenia on chromosome 1q21-22 in large families from eastern Canada [Brzustowicz et al., 2000: Science 288:678-682]. We did not reproduce such a finding in large pedigrees of eastern Québec based on seven markers spanning the 1p13-1q22 region and using both the models and phenotypes of Brzustowicz et al. and those used in our ongoing genome scan in 21 large French Canadian families. There was no significant total LOD scores in that chromosomal region (a maximum of 0.57) either for schizophrenia or bipolar disorders, nor any signal in individual large pedigrees. However, the samples of Brzustowicz et al. and ours differed in terms of their origins, the latter being of French ancestry and the former of Celtic and German descent. Population difference, genetic heterogeneity, and differences in ascertainment might explain the lack of replication. The result reported by Brzustowicz et al. cannot be discarded and should probably be considered as a susceptibility locus for a subset of the schizophrenic population.