Schizophrenia susceptibility and chromosome 6p24–22

Sir-Diehl and co-workers reported a lod score of 3.0 for linkage of schizophrenia to a chromosome 6 marker closely linked to the SCA1 locus, with one of several models tested in a sample of pedigrees from Ireland, but failed to replicate this finding in 56 U.S. pedigrees. An analysis of the entire Irish cohort of 265 pedigrees (published in this issue, but initially a personal communication by Kendler, Straub and MacLean to investigators in the field) resulted in a maximum lod score under the admixture test for linkage with heterogeneity of 3.4, with 15% of pedigrees linked, 2 centimorgans (cM) from D6S296, when using the 'PEN' model, a co-dominant model with incomplete penetrance, and a broadly defined disease phenotype. In another analysis of the Irish sample (186 pedigrees), Wang et al. obtained a maximum multipoint lod score of 3.9, assuming 50% of families linked, when the F13A locus and D6S260 were analysed using the PEN model. Multilocus affected pedigree member analyses involving D6S260 and markers to either side of it (D6S259 and D6S285) supported this finding. We report here the analysis of the 6p24-22 markers D6S296, D6S470, D6S259 and D6S285 in 45 pedigrees multiply affected with schizophrenia and related disorders using our two (dominant, recessive) weighted screening models, and the PEN model.