Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a susceptibility locus for schizophrenia and psychosis.
Schizophrenia is a common psychiatric disorder with a complex genetic etiology. To understand the genetic basis of this syndrome in Portuguese Island populations, we performed a genome-wide scan of 29 families with schizophrenia, which identified a single region on 5q31-5q35 with strong linkage (NPL=3.09, P=0.0012 at D5S820). Empirical simulations set a genome-wide threshold of NPL=3.10 for significant linkage. Additional support for this locus in schizophrenia comes from higher-density mapping and mapping of 11 additional families. The combined set of 40 families had a peak NPL=3.28 (P=0.00066) at markers D5S2112-D5S820. These data and previous linkage findings from other investigators provide strong and consistent evidence for this genomic region as a susceptibility locus for schizophrenia. Exploratory analyses of a novel phenotype, psychosis, in families with schizophrenia and bipolar disorder detected evidence for linkage to the same markers as found in schizophrenia (peak NPL=3.03, P=0.0012 at D5S820), suggesting that this locus may be responsible for the psychotic symptoms observed in both diseases. Molecular Psychiatry (2004) 9, 213-218. doi:10.1038/sj.mp.4001418 Published online 30 December 2003
Sklar
P
P
Department of Psychiatry, Harvard Medical School, and Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA. sklar@psych.mgh.harvard.edu
Pato
M T
MT
Kirby
A
A
Petryshen
T L
TL
Medeiros
H
H
Carvalho
C
C
Macedo
A
A
Dourado
A
A
Coelho
I
I
Valente
J
J
Soares
M J
MJ
Ferreira
C P
CP
Lei
M
M
Verner
A
A
Hudson
T J
TJ
Morley
C P
CP
Kennedy
J L
JL
Azevedo
M H
MH
Lander
E
E
Daly
M J
MJ
Pato
C N
CN
D001394:Azores; D001714:Bipolar Disorder / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D012559:Schizophrenia / Q000235:genetics*