A Transmission Disequilibrium and Linkage Analysis of D22s278 Marker Alleles in 574 Families: Further Support for a Susceptibility Locus for Schizophrenia at 22q12

Previously, a combined analysis by the Chromosome 22 Collaborative Linkage Group (1996; Am. J. Med Genet. 67, 40- 45) used an affected sib- pair analysis of a single marker ( D 22S278) in 574 families multiply affected by schizophrenia and found some evidence for linkage (chi(2)=9.35 , 1 df, p=0 . 001), suggesting the presence of a disease locus nearby on chromosome 22q12. In order to further investigate the importance of this result, we have performed the transmission disequilibrium test (TDT) and additional parametric and non-parametric linkage analysis of the same data . The most positive result obtained was an admixture lod score of 0.9 under the assumption of locus heterogeneity and dominant transmission. The result of the TDT analysis was significant at p=0.015 (allele-wise; chi(2 )=22, 10 df) and p=0.00016 (genotype-wise; chi(2)=66.2, 30 df, empirical p value=0.0009). Overall, these results further strengthen the notion that there is a susceptibility locus for schizophrenia close to D22S278. (C) 1998 Published by Elsevier Science B.V. All rights reserved