神经发育性疾病病因复杂,由遗传和环境因素共同决定,其中遗传因素起重要作用。基于致病基因的研究是认识疾病的生物学基础的重要方法。锌指蛋白804A(zinc finger protein 804A,ZNF804A)是基于"常见疾病,常见变异"假说而开展...神经发育性疾病病因复杂,由遗传和环境因素共同决定,其中遗传因素起重要作用。基于致病基因的研究是认识疾病的生物学基础的重要方法。锌指蛋白804A(zinc finger protein 804A,ZNF804A)是基于"常见疾病,常见变异"假说而开展的全基因组关联研究发现的与精神疾病相关性最强的易感基因之一,受到了研究者的极大关注。本文将对ZNF804A在精神分裂症和孤独谱系障碍等神经发育性疾病中的研究进展做一综述。展开更多
The ZNF804 A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting sta...The ZNF804 A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting state and in patients with schizophrenia remains unclear. In this study, we investigated the ZNF804 A polymorphism at rs1344706 in 92 schizophrenic patients and 99 healthy controls of Han Chinese descent, and used resting-state functional magnetic resonance imaging to explore the functional connectivity in the participants. We found a significant main effect of genotype on the resting-state functional connectivity（RSFC） between the hippocampus and the dorsolateral prefrontal cortex（DLPFC） in both schizophrenic patients and healthy controls. The homozygous ZNF804 A rs1344706 genotype（AA） conferred a high risk of schizophrenia, and also exhibited significantly decreased resting functional coupling between the left hippocampus and right DLPFC（F（2,165） = 13.43,P ／ 0.001）. The RSFC strength was also correlated with cognitive performance and the severity of psychosis in schizophrenia. The current findings identified the neural impact of the ZNF804 A rs1344706 on hippocampalprefrontal RSFC associated with schizophrenia.展开更多
Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism（SNP） rs1344706 in the gene ZNF804 A encoding zinc finger protein 804 A was...Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism（SNP） rs1344706 in the gene ZNF804 A encoding zinc finger protein 804 A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of Pub Med database identified 25 case–control studies with available genotype frequencies of rs1344706 for the meta-analysis,involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio（OR） with 95% confidence interval（CI） was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations（P = 0.028, OR = 1.138, 95% CI：1.014–1.278; P = 0.004 for heterogeneity） and Asian populations（P = 0.008, OR = 1.092, 95%CI： 1.023–1.165; P = 0.001 for heterogeneity）, but not in other populations（P = 0.286,OR = 1.209, 95% CI： 0.853–1.714, P = 0.120 for heterogeneity）. Egger’s test（P 〉 0.05） and Begg’s test（P 〉 0.05） are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.展开更多
文摘神经发育性疾病病因复杂,由遗传和环境因素共同决定,其中遗传因素起重要作用。基于致病基因的研究是认识疾病的生物学基础的重要方法。锌指蛋白804A(zinc finger protein 804A,ZNF804A)是基于"常见疾病,常见变异"假说而开展的全基因组关联研究发现的与精神疾病相关性最强的易感基因之一,受到了研究者的极大关注。本文将对ZNF804A在精神分裂症和孤独谱系障碍等神经发育性疾病中的研究进展做一综述。
基金supported by the National Key Research and Development Program of China (2016YFC1307000 and 2015BAI13B01)the National Natural Science Foundation of China (91432304, 81370032, 81571313 and 81221002)+1 种基金Capital Health Development Research (2016-2-4112)Beijing Nova Program Interdisciplinary Studies Cooperative Project (Z161100004916038)
文摘The ZNF804 A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting state and in patients with schizophrenia remains unclear. In this study, we investigated the ZNF804 A polymorphism at rs1344706 in 92 schizophrenic patients and 99 healthy controls of Han Chinese descent, and used resting-state functional magnetic resonance imaging to explore the functional connectivity in the participants. We found a significant main effect of genotype on the resting-state functional connectivity（RSFC） between the hippocampus and the dorsolateral prefrontal cortex（DLPFC） in both schizophrenic patients and healthy controls. The homozygous ZNF804 A rs1344706 genotype（AA） conferred a high risk of schizophrenia, and also exhibited significantly decreased resting functional coupling between the left hippocampus and right DLPFC（F（2,165） = 13.43,P ／ 0.001）. The RSFC strength was also correlated with cognitive performance and the severity of psychosis in schizophrenia. The current findings identified the neural impact of the ZNF804 A rs1344706 on hippocampalprefrontal RSFC associated with schizophrenia.
基金financially supported by the Science and Technology Innovation Project of Yunnan Province, China (Grant No. 2011DH011)Educational Commission of Yunnan Province, China (Grant No. 2013J064)
文摘Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism（SNP） rs1344706 in the gene ZNF804 A encoding zinc finger protein 804 A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of Pub Med database identified 25 case–control studies with available genotype frequencies of rs1344706 for the meta-analysis,involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio（OR） with 95% confidence interval（CI） was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations（P = 0.028, OR = 1.138, 95% CI：1.014–1.278; P = 0.004 for heterogeneity） and Asian populations（P = 0.008, OR = 1.092, 95%CI： 1.023–1.165; P = 0.001 for heterogeneity）, but not in other populations（P = 0.286,OR = 1.209, 95% CI： 0.853–1.714, P = 0.120 for heterogeneity）. Egger’s test（P 〉 0.05） and Begg’s test（P 〉 0.05） are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.
