NCAM1 and neurocognition in schizophrenia.
BACKGROUND
Alterations in neurocognition may be fundamental to schizophrenia and may be endophenotypes. Neural cell adhesion molecule 1 (NCAM1, aliases NCAM and CD56) may be a candidate gene for schizophrenia or for neurocognition in schizophrenia as supported by linkage and functional findings.


METHODS
Subjects were 641 patients with schizophrenia who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) clinical trial. Neurocognition was assessed at study baseline. Nine NCAM1 single nucleotide polymorphisms (SNPs) were blindly genotyped. Analysis of covariance was used to test for single SNP associations and haplotype regression for multilocus associations.


RESULTS
As there were suggestions of population stratification, all analyses were conducted stratified by inferred ancestry. In the "Europe only" stratum, there were nominally significant associations with five contiguous SNPs (rs1943620, rs1836796, rs1821693, rs686050, rs584427) with the strongest association at rs1836796 (p = .007). Via permutation testing, the probability of obtaining five consecutive statistically significant SNPs with p-values <or= .05 was p = .0044. These results were robust to examination of model assumptions. Haplotype analyses did not identify significant haplotype associations.


CONCLUSIONS
Although it is essential to see if these findings replicate in additional samples, we suggest that NCAM1 deserves further scrutiny for its relevance to clinical and etiological aspects of schizophrenia.
Sullivan
Patrick F
PF
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA. pfsulliv@med.unc.edu
Keefe
Richard S E
RS
Lange
Leslie A
LA
Lange
Ethan M
EM
Stroup
T Scott
TS
Lieberman
Jeffrey
J
Maness
Patricia F
PF
D000328:Adult; D000704:Analysis of Variance; D003071:Cognition / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D044465:White People
D019006:Neural Cell Adhesion Molecules