Variation in psychosis gene ZNF804A is associated with a refined schizotypy phenotype but not neurocognitive performance in a large young male population.
Variation in psychosis gene ZNF804A is associated with a refined schizotypy phenotype but not neurocognitive performance in a large young male population.
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DOI：
10.1093/schbul/sbs110
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发表时间：
2013-11
影响因子：
6.6
通讯作者：
Straub RE
中科院分区：
文献类型：
--
作者：
Stefanis NC;Hatzimanolis A;Avramopoulos D;Smyrnis N;Evdokimidis I;Stefanis CN;Weinberger DR;Straub RE
最近发现ZNF 804 A基因的遗传变异与精神分裂症和双相情感障碍有关，尽管该基因可能带来风险的途径在很大程度上仍然未知。我们着手调查是否共同ZNF 804 A变异影响精神病相关的中间表型，如认知性能依赖于前额叶和额颞叶脑功能，autootypal性状，并在一个大的年轻男性人口衰减精神病的经验。使用所有4个可用的自评型问卷和回顾性地从精神病倾向和精神分裂症发病率的雅典研究（ASPIS）中提取的认知数据进行关联分析。对1507名健康入伍青年的DNA样本进行了ZNF 804 A基因座4个多态性标记的基因分型。单标记物分析显示，最近发现的2个候选精神分裂症易感性变异体（rs 1344706和rs7597593）与主要以自评妄想症/参考想法为特征的精确阳性精神分裂症表型之间存在显著关联。注意到与所有阳性但非阴性的异型性相关因素的名义关联。ZNF 804 A基因型对偏执的影响在单倍型水平得到证实。与持续注意力或工作记忆表现的中央指标没有显著关联。在这项研究中，ZNF 804 A变异与基于人群的自评型表型相关，以前建议优先反映精神病的遗传易感性，并通过误解其他中性社会线索和感知经验的倾向来定义，在一个人的直接环境中，作为个人相关和重要的信息。这表明一种新的途径，精神分裂症牵连ZNF 804 A遗传变异可能会赋予临床精神病在一般人群水平的风险。
Genetic variability within the ZNF804A gene has been recently found to be associated with schizophrenia and bipolar disorder, although the pathways by which this gene may confer risk remain largely unknown. We set out to investigate whether common ZNF804A variants affect psychosis-related intermediate phenotypes such as cognitive performance dependent on prefrontal and frontotemporal brain function, schizotypal traits, and attenuated psychotic experiences in a large young male population. Association analyses were performed using all 4 available self-rated schizotypy questionnaires and cognitive data retrospectively drawn from the Athens Study of Psychosis Proneness and Incidence of Schizophrenia (ASPIS). DNA samples from 1507 healthy young men undergoing induction to military training were genotyped for 4 previously studied polymorphic markers in the ZNF804A gene locus. Single-marker analysis revealed significant associations between 2 recently identified candidate schizophrenia susceptibility variants (rs1344706 and rs7597593) and a refined positive schizotypy phenotype characterized primarily by self-rated paranoia/ideas of reference. Nominal associations were noted with all positive, but not negative, schizotypy related factors. ZNF804A genotype effect on paranoia was confirmed at the haplotype level. No significant associations were noted with central indexes of sustained attention or working memory performance. In this study, ZNF804A variation was associated with a population-based self-rated schizotypy phenotype previously suggested to preferentially reflect genetic liability to psychosis and defined by a tendency to misinterpret otherwise neutral social cues and perceptual experiences in one’s immediate environment, as personally relevant and significant information. This suggests a novel route by which schizophrenia-implicated ZNF804A genetic variation may confer risk to clinical psychosis at the general population level.
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DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
11.3
作者：
CORNBLATT, BA;RISCH, NJ;ERLENMEYERKIMLING, L
通讯作者：
ERLENMEYERKIMLING, L
影响因子：
4.6
作者：
CHAPMAN, LJ;CHAPMAN, JP;RAULIN, ML
通讯作者：
RAULIN, ML
影响因子：
2.1
作者：
Clarke, Geraldine M.;Cardon, Lon R.
通讯作者：
Cardon, Lon R.
DOI：
10.1002/ajmg.b.31156
发表时间：
2011-03-01
影响因子：
2.8
作者：
Schanze, D.;Ekici, A. B.;Stoeber, G.
通讯作者：
Stoeber, G.