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, 1 0p, and 13q were investigated for genetic linkage with mapped markers with an average spacing of 5.64 cM. We studied 734 informative multiplex pedigre es (824 independent affected sibling pairs [ASPs], or 1,003 ASPs when all p ossible pairs are counted), which were collected in eight centers. Cases wi th diagnoses of schizophrenia or schizoaffective disorder (DSM-IIIR criteri a) were considered affected (n = 1,937). Data were analyzed with multipoint methods, including nonparametric linkage (NPL), ASP analysis using the pos sible-triangle method, and logistic-regression analysis of identity-by-desc ent (IBD) sharing in ASPs with sample as a covariate, in a test for intersa mple heterogeneity and for linkage with allowance for intersample heterogen eity. The data most supportive for linkage to schizophrenia were from chrom osome 6q; logistic-regression analysis of linkage allowing for intersample heterogeneity produced an empirical P value < .0002 with, or P = .0004 with out, inclusion of the sample that produced the first positive report in thi s region; the maximum Nm,score in this region was 2.47 (P = .0046), the max imum 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, w ith logistic-regression analysis of linkage producing an empirical P = .045 and with significant evidence for intersample heterogeneity (empirical P = .0096).