Genome Scan of Schizophrenia Families in a Large Veterans Affairs Cooperative Study Sample: Evidence for Linkage to 18p11.32 and for Racial Heterogeneity on Chromosomes 6 and 14

Departments of Pharmacology, Neurology, and Medicine, University of Washington, Seattle, WashingtonGenome-wide linkage analyses of schizophreniahave identified several regions that may harborschizophrenia susceptibility genes but, given thecomplexetiologyofthedisorder,itisunlikelythatall susceptibility regions have been detected. Wereport results from a genome scan of 166 schizo-phrenia families collected through the Depart-ment of Veterans Affairs Cooperative StudiesProgram. Our definition of affection statusincluded schizophrenia and schizoaffective dis-order, depressed type and we defined families asEuropean American (EA) and African American(AA) based on the probands’ and parents’ racesbased on data collected by interviewing theprobands. We also assessed evidence for racialheterogeneity in the regions most suggestive oflinkage. The maximum LOD score across thegenome was 2.96 for chromosome 18, at 0.5 cM inthe combined race sample. Both racial groupsshowed LOD scores greater than 1.0 for chromo-some 18. The empirical P-value associated withthat LOD score is 0.04 assuming a single genomescan for the combined sample with race narrowlydefined, and 0.06 for the combined sample allow-ing for broad and narrow definitions of race. Theempirical P-value of observing a LOD score aslarge as 2.96 in the combined sample, and of atleast 1.0 ineach racialgroup, allowing for narrowand broad racial definitions, is 0.04. Evidence forthe second and third largest linkage signals comesolely from the AA sample on chromosomes 6(LOD¼2.11 at 33.2 cM) and 14 (LOD¼2.13 at51.0). The linkage evidence differed between theAAandEAsamples(chromosome6P-value¼0.007and chromosome 14 P-value¼0.004).