Linkage and linkage disequilibrium of a dense map of 1q21-23 markers in schizophrenia families from the azores, Portugal and Canada

More than ten genome-wide scans have indicated several chromosomal regions promising to contain genes that increase the risk for schizophrenia. Evidence for linkage on 1q21-23 in a region of approximately 10 cM was shown in at least four study from different data sets. We tested for linkage and linkage disequilibrium this 10 cM region of the long arm of 1q21-23. We genotyped 11 markers and the CAG repeat in the small conductance K channel Ca⁺⁺ activated Gene (KCNN3) in a collection of families from the geographically isolated population of the Portuguese Azores islands, from Portugal Mainland and from Canada. A total of 96 families of 138 schizophrenia subjects from Portugal and 45 triads collected from the Toronto area were available. Non parametric two point linkage analysis on the affected sib pairs from the Azores revealed the highest NPL of 1.4 for the marker D1S1677. No linkage disequilibrium was found for any of the marker studied. The TDT analysis for individual alleles shows an intriguing biased transmission of the allele with 14 repeats in the Portuguese families (Chi-squared = 7.1, 1df; P =.007) that however was not replicated in the triads from Canada. It is unlikely that a gene with a major contribution to schizophrenia is on 1q21-23 in our samples.