Stefanis Nicholas C, Trikalinos Thomas A, Avramopoulos Dimitrios, Smyrnis Nikos, Evdokimidis Ioannis, Ntzani Evangelia E, Ioannidis John P, Stefanis Costas N
University Mental Health Research Institute, National and Kapodistrian University of Athens, Athens, Greece.
Biol Psychiatry. 2007 Oct 1;62(7):784-92. doi: 10.1016/j.biopsych.2006.11.015. Epub 2007 Mar 6.
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.
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.
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.
The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.
认知功能和精神分裂症型人格的某些方面已被提出作为精神分裂症潜在的内表型。尚不清楚这些内表型在群体水平上的表达是否受精神分裂症候选易感基因的遗传变异性调节。
我们在2243名年轻男性应征入伍者的代表性群体中，研究了DTNBP1、NRG1、DAOA/G32和DAAO基因内18个单核苷酸多态性（SNP）对认知和自评精神分裂症型人格的潜在影响。评估了单个SNP和单倍型关联。
DTNBP1基因的SNP rs2619522和rs760761表现出几种单标记关联，次要等位基因与较低的注意力容量相关，但也与阳性和偏执型精神分裂症型人格得分降低有关。DTNBP1单倍型负荷与非言语智商、偏执型精神分裂症型人格和持续注意力存在临界关联。对于单个NRG1多态性，观察到与持续注意力和工作记忆有孤立但微弱的关联信号，但与精神分裂症型人格无关。功能性SNP8NRG243177的风险等位基因与空间工作记忆容量降低有关。观察到DAAO单倍型变异性对阴性和紊乱型精神分裂症型人格有孤立影响。未检测到DAOA/G32变异性有令人信服地关联。
DTNBP1以及程度较轻的NRG1和DAAO变异可能在群体水平上对精神分裂症内表型发挥基因特异性调节作用。
