Abstract
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A sample of 71 sib-pair families with schizophrenia has been collected for genome-wide linkage studies. Both parents could be genotyped in 66 families, for four families with one missing parent, genotypes could be reconstructed from unaffected siblings. Thus, we have been able to apply the TDT. We used a version of sib_tdt implemented in ASPEX which calculates empirical probabilities for chi-squared statistics, and reflects association independent of linkage within families. We tested the 486 markers mainly microsatellites originally genotyped for genome-wide linkage analysis. The average marker distance was about 10cM, but 1-2cM in regions with a priori evidence for linkage. There were 22 markers with p (0.05) and 7 markers with p (0.01). There was no marker with a p value <0.001 reaching the conservatively estimated significance level of 0.0001 (0.05/486) given by multiple testing. However, we had previously found evidence for linkage to D10S211 (p = 0.03) and GOLF (p = 0.0032). In addition, GOLF can be considered as a candidate gene. For D8S258 (p = 0.01) linkage data exists in other family samples, but interestingly not in our sample. The detection of linkage disequilibrium on chromosome 8, 10, and 18 (GOLF) may provide starting points for searching candidate genes. (Supported by Deutsche Forschungsgemeinschaft and a grant from the German-Israeli Foundation).