Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21

JL Blouin, BA Dombroski, SK Nath, VK Lasseter… - Nature …, 1998 - nature.com
JL Blouin, BA Dombroski, SK Nath, VK Lasseter, PS Wolyniec, G Nestadt, M Thornquist…
Nature genetics, 1998nature.com
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 …
Abstract
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).
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