Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21

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Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established1. 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 heterogeneity3,6. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia7,8, 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).

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Figure 1: Genome-wide scan for schizophrenia susceptibility loci (SSLs).
Figure 2: Multipoint non-parametric and parametric analyses for chromosome 8 (a) and chromosome 13 (b) from a genome-wide scan for SSLs.


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This work was supported by funding from Novartis Pharmaceuticals (1995-1998), grants from the National Institutes of Mental Health (NIMH; 1989-1995; R01 MH-45588 and 1 R01 35712), the National Institutes of Health (NIH) grant DRR-OPD-GCRC RR00722, the National Alliance for Research on Schizophrenia and Depression and gifts from private foundations and private donors. We wish to thank the patients and their families and the mental health professionals who referred patients and provided information.

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Correspondence to Ann E. Pulver.

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