Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level.
BACKGROUND
Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia.


METHODS
We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1, NRG1, DAOA/G32, and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated.


RESULTS
The DTNBP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. The DTNBP1 haplotype load had borderline associations with nonverbal IQ, paranoid schizotypy, and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected.


CONCLUSIONS
The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.
Stefanis
Nicholas C
NC
University Mental Health Research Institute, National and Kapodistrian University of Athens, Athens, Greece. nistefan@med.uoa.gr
Trikalinos
Thomas A
TA
Avramopoulos
Dimitrios
D
Smyrnis
Nikos
N
Evdokimidis
Ioannis
I
Ntzani
Evangelia E
EE
Ioannidis
John P
JP
Stefanis
Costas N
CN
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D004247:DNA / Q000235:genetics; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007361:Intelligence Tests; D047908:Intracellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics / Q000502:physiology; D009483:Neuropsychological Tests; D010556:Personality Tests; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011153:Population; D012306:Risk; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D012569:Schizotypal Personality Disorder / Q000235:genetics* / Q000523:psychology*
D002352:Carrier Proteins; C475071:DAOA protein, human; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020890:Neuregulin-1; D004247:DNA