OBJECTIVE: This study was an attempt to replicate evidence for a vulnerability locus for schizophrenia and associated disorders in the 8p22-21 region reported by Pulver and colleagues. METHOD: The linkage sample of the Irish Study of High-Density Schizophrenia Families consists of 265 multiplex families containing 1,408 individuals. Fifteen markers covering 30 centimorgans on chromosome 8p were tested. Three statistical methods were used: two-point and multipoint heterogeneity lod scores and a multipoint nonparametric test. RESULTS: According to two-point heterogeneity lod scores, the strongest evidence for linkage was found for markers D8S1731 (maximum lod score = 2.00), D8S1715 (maximum lod score = 2.52), and D8S133 (maximum lod score = 2.08) by assuming a phenotypic definition of all psychiatric illness and a range of genetic models. According to multipoint heterogeneity lod scores, the strongest evidence for linkage (maximum lod score = 2.34), found by using a dominant genetic model and a broad definition of the schizophrenia spectrum, extended over a 10-cM region between markers D8S1715 and D8S1739. Multipoint nonparametric linkage found the strongest evidence (maximum z = 2.51) over a broader region when either a diagnosis of core schizophrenia or a narrow definition of the schizophrenia spectrum was used. This putative vulnerability locus was segregating in 10%-25% of the families studied. CONCLUSIONS: This study supports the existence of a vulnerability locus for schizophrenia on chromosome 8p. In this sample, this locus appears to influence the risk of illness in only a modest proportion of families and predisposes to a range of schizophrenia spectrum and possibly nonspectrum disorders.
OBJECTIVE: This study was an attempt to replicate evidence for a vulnerability locus for schizophrenia and associated disorders in the 8p22-21 region reported by Pulver and colleagues. METHOD: The linkage sample of the Irish Study of High-Density Schizophrenia Families consists of 265 multiplex families containing 1,408 individuals. Fifteen markers covering 30 centimorgans on chromosome 8p were tested. Three statistical methods were used: two-point and multipoint heterogeneity lod scores and a multipoint nonparametric test. RESULTS: According to two-point heterogeneity lod scores, the strongest evidence for linkage was found for markers D8S1731 (maximum lod score = 2.00), D8S1715 (maximum lod score = 2.52), and D8S133 (maximum lod score = 2.08) by assuming a phenotypic definition of all psychiatric illness and a range of genetic models. According to multipoint heterogeneity lod scores, the strongest evidence for linkage (maximum lod score = 2.34), found by using a dominant genetic model and a broad definition of the schizophrenia spectrum, extended over a 10-cM region between markers D8S1715 and D8S1739. Multipoint nonparametric linkage found the strongest evidence (maximum z = 2.51) over a broader region when either a diagnosis of core schizophrenia or a narrow definition of the schizophrenia spectrum was used. This putative vulnerability locus was segregating in 10%-25% of the families studied. CONCLUSIONS: This study supports the existence of a vulnerability locus for schizophrenia on chromosome 8p. In this sample, this locus appears to influence the risk of illness in only a modest proportion of families and predisposes to a range of schizophrenia spectrum and possibly nonspectrum disorders.
Authors: H M Gurling; G Kalsi; J Brynjolfson; T Sigmundsson; R Sherrington; B S Mankoo; T Read; P Murphy; E Blaveri; A McQuillin; H Petursson; D Curtis Journal: Am J Hum Genet Date: 2001-03 Impact factor: 11.025
Authors: M Daniele Fallin; Virginia K Lasseter; Paula S Wolyniec; John A McGrath; Gerald Nestadt; David Valle; Kung-Yee Liang; Ann E Pulver Journal: Am J Hum Genet Date: 2003-08-15 Impact factor: 11.025
Authors: Hreinn Stefansson; Engilbert Sigurdsson; Valgerdur Steinthorsdottir; Soley Bjornsdottir; Thordur Sigmundsson; Shyamali Ghosh; Jon Brynjolfsson; Steinunn Gunnarsdottir; Omar Ivarsson; Thomas T Chou; Omar Hjaltason; Birgitta Birgisdottir; Helgi Jonsson; Vala G Gudnadottir; Elsa Gudmundsdottir; Asgeir Bjornsson; Brynjolfur Ingvarsson; Andres Ingason; Sigmundur Sigfusson; Hronn Hardardottir; Richard P Harvey; Donna Lai; Mingdong Zhou; Daniela Brunner; Vincent Mutel; Acuna Gonzalo; Greg Lemke; Jesus Sainz; Gardar Johannesson; Thorkell Andresson; Daniel Gudbjartsson; Andrei Manolescu; Michael L Frigge; Mark E Gurney; Augustine Kong; Jeffrey R Gulcher; Hannes Petursson; Kari Stefansson Journal: Am J Hum Genet Date: 2002-07-23 Impact factor: 11.025