Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample

• Published in: American journal of medical genetics 2001-12, Vol.105 (8), p.662-668
• Main Authors: Tsuang, Debby W., Skol, Andrew D., Faraone, Stephen V., Bingham, Stephen, Young, Keith A., Prabhudesai, Sarita, Haverstock, Susan L., Mena, Felicitas, Menon, A. Shrikumar, Bisset, Darren, Pepple, John, Sauter, Fred, Baldwin, Charlene, Weiss, David, Collins, Joseph, Boehnke, Michael, Schellenberg, Gerard D., Tsuang, Ming T.
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; alpha7 Nicotinic Acetylcholine Receptor; Biological and medical sciences; chromosome 15; Chromosomes, Human, Pair 15 - genetics; DNA - genetics; Family Health; Female; Genetic Linkage; genetics; Genotype; Humans; linkage; Lod Score; Male; Medical sciences; Microsatellite Repeats; Middle Aged; nicotinic cholinergic receptor; Pedigree; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Receptors, Nicotinic - genetics; Schizophrenia; Schizophrenia - genetics; Veterans
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/ajmg.1550

Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage 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 affected subjects and 216 affected sibling pairs. By DSM‐III‐R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo‐affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American 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 for the region surrounding the α‐7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds‐only linkage analysis. In the European American families, there was a maximum Z‐score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA‐7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds. © 2001 Wiley‐Liss, Inc.