Evidence for a role of the NOS1AP (CAPON) gene in schizophrenia and its clinical dimensions: an association study in a South American population isolate.
OBJECTIVE
Recent studies have implicated a region on chromosome 1q21-23, including the NOS1AP gene, in susceptibility to schizophrenia. However, replication studies have been inconsistent, a fact that could partly relate to the marked psychopathological heterogeneity of schizophrenia. The aim of this study is to evaluate association of polymorphisms in the NOS1AP gene region to schizophrenia, in patients from a South American population isolate, and to assess if these variants are associated with specific clinical dimensions of the disorder.


METHODS
We genotyped 24 densely spaced SNPs in the NOS1AP gene region in a schizophrenia trio sample. The transmission disequilibrium test (TDT) was applied to single marker and haplotype data. Association to clinical dimensions (identified by factor analysis) was evaluated using a quantitative transmission disequilibrium test (QTDT).


RESULTS
We found significant association between eight SNPs in the NOS1AP gene region to schizophrenia (minimum p value = 0.004). The QTDT analysis of clinical dimensions revealed an association to a dimension consisting mainly of negative symptoms (minimum p value 0.001).


CONCLUSIONS
Our findings are consistent with a role for NOS1AP in susceptibility to schizophrenia, especially for the 'negative syndrome' of the disorder.
Kremeyer
Barbara
B
The Galton Laboratory, Department of Biology, University College London, London, UK.
García
Jenny
J
Kymäläinen
Hanna
H
Wratten
Naomi
N
Restrepo
Gabriel
G
Palacio
Carlos
C
Miranda
Ana Lucía
AL
López
Carlos
C
Restrepo
Margarita
M
Bedoya
Gabriel
G
Brzustowicz
Linda M
LM
Ospina-Duque
Jorge
J
Arbeláez
María Patricia
MP
Ruiz-Linares
Andrés
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D005163:Factor Analysis, Statistical; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013020:South America; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; C488081:NOS1AP protein, human