TY - JOUR
T1 - Impact of Schizophrenia Candidate Genes on Schizotypy and Cognitive Endophenotypes at the Population Level
AU - Stefanis, Nicholas C.
AU - Trikalinos, Thomas A.
AU - Avramopoulos, Dimitrios
AU - Smyrnis, Nikos
AU - Evdokimidis, Ioannis
AU - Ntzani, Evangelia E.
AU - Ioannidis, John P.
AU - Stefanis, Costas N.
N1 - Funding Information:
This work was supported by the Grant EKBAN 97 to NCS from the General Secretariat of Research and Technology of the Greek Ministry of Development. Intrasoft provided the technical support for this project.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - 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.
AB - 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.
KW - Cognition
KW - DAAO
KW - DAOA/G32
KW - DTNBP1
KW - NRG1
KW - endophenotype
KW - schizophrenia
KW - schizotypy
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U2 - 10.1016/j.biopsych.2006.11.015
DO - 10.1016/j.biopsych.2006.11.015
M3 - Article
C2 - 17336946
AN - SCOPUS:34548499070
SN - 0006-3223
VL - 62
SP - 784
EP - 792
JO - Biological psychiatry
JF - Biological psychiatry
IS - 7
ER -