title: Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families.
abstract: 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.
  
  
  METHODS
  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.affiliation: Departments of Psychiatry and Human Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0126, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Kendler
authors.forename: C J
authors.initials: CJ
authors.lastname: MacLean
authors.forename: F A
authors.initials: FA
authors.lastname: O'Neill
authors.forename: J
authors.initials: J
authors.lastname: Burke
authors.forename: B
authors.initials: B
authors.lastname: Murphy
authors.forename: F
authors.initials: F
authors.lastname: Duke
authors.forename: R
authors.initials: R
authors.lastname: Shinkwin
authors.forename: S M
authors.initials: SM
authors.lastname: Easter
authors.forename: B T
authors.initials: BT
authors.lastname: Webb
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Walsh
authors.forename: R E
authors.initials: RE
authors.lastname: Straub
mesh_terms: D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005190:Family; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*
chemical_list: D005819:Genetic Markers