Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21

Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established 1 . Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2 ), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity 3 , 6 . Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia 7 , 8 , and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9 , 10 , 11 , 12 , 13 ). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score = 4.18; P = 0.00002), and suggestive evidence for another SSL on chromosome 8p21–22 (NPL = 3.64; P = 0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL = 2.57; P = 0.005), 7q11 (NPL = 2.50, P = 0.007) and 22q11 (NPL = 2.42, P = 0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL = 2.36, P = 0.007) and supported the SSL in 8p22-p21 (NPL = 1.95, P = 0.023).