Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families.
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.
Kendler
K S
KS
Departments of Psychiatry and Human Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0126, USA.
MacLean
C J
CJ
O'Neill
F A
FA
Burke
J
J
Murphy
B
B
Duke
F
F
Shinkwin
R
R
Easter
S M
SM
Webb
B T
BT
Zhang
J
J
Walsh
D
D
Straub
R E
RE
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*
D005819:Genetic Markers