Examination of genetic linkage of chromosome 15 to schizophrenia in a large veterans affairs cooperative study sample

Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkag e analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled aff ected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 s ubjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classif ied as schizo-affective disorder, depressed. Participating families had div erse ethnic backgrounds. The largest single group were northern European Am erican families (n = 62, 37%), but a substantial proportion was African Ame rican kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM f or the region surrounding the alpha -7 nicotinic cholinergic receptor subun it gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American fa milies, there was a maximum Z-score of 1.65 between markers D15S165 and D15 S1010. These markers are within 1 cM from CHRNA-7, the site previously impl icated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds. Published 2001 Wiley-Liss, Inc.(da gger).