Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: Schizophrenia linkage collaborative group III

Schizophrenia candidate regions 33-51 cM in length on chromosomes 5q, 6q, 10p, and 13q were investigated for genetic linkage with mapped markers with an average spacing of 5.64 cM. We studied 734 informative multiplex pedigrees (824 independent affected sibling pairs [ASPs], or 1,003 ASPs when all possible pairs are counted), which were collected in eight centers. Cases with diagnoses of schizophrenia or schizoaffective disorder (DSM-IIIR criteria) were considered affected (n = 1,937). Data were analyzed with multipoint methods, including nonparametric linkage (NPL), ASP analysis using the possible-triangle method, and logistic-regression analysis of identity-by-descent (IBD) sharing in ASPs with sample as a covariate, in a test for intersample heterogeneity and for linkage with allowance for intersample heterogeneity. The data most supportive for linkage to schizophrenia were from chromosome 6q; logistic-regression analysis of linkage allowing for intersample heterogeneity produced an empirical P value < .0002 with, or P = .0004 without, inclusion of the sample that produced the first positive report in this region; the maximum Nm,score in this region was 2.47 (P = .0046), the maximum LOD score (MLS) from ASP analysis was 3.10 (empirical P = .0036), and there was significant evidence for intersample heterogeneity (empirical P = .0038). More-modest support for linkage was observed for chromosome 10p, with logistic-regression analysis of linkage producing an empirical P = .045 and with significant evidence for intersample heterogeneity (empirical P = .0096).