Published: 2022-07-27

ZNF804A variants relation to schizophrenia: a systematic review

Ahmed M. Alsheikh


Schizophrenia is a devastating mental disease; its etiology isn't clearly understood. However, several hypotheses have been suggested; one of them is the involvement of the genetic factor. Rare and common variants of deoxyribonucleic acid (DNA) genes may contribute to the development of schizophrenia. ZNF804A is a gene encoding for zinc-finger protein, which has been reported to be associated with schizophrenia. However, a few recent studies were conducted on such subject, and there was no systematic analysis for such association. This study assessed the relation between ZNF804A variants and schizophrenia by reviewing the previous studies concerned with such subject. This systematic review was according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist guidance for systematic review includes Pubmed, Embase, and Medline databases were used for searching for published articles between 2015 and 2021. The inclusion criteria were original articles conducted on schizophrenia patients, English, and full text- articles. As well as study the association between SCZ and ZNF804A variants. A total of 408 articles were obtained, only six articles were eligible for the inclusion criteria. The included studies involved a total number of 4,579 of them there were 2,738 schizophrenia patients and was conducted on four populations. All studies reported rs1344706 of the ZNF804A gene. The association between rs1344706 of the ZNF804A gene and SCZ was found in four studies out of the six studies, whereas the other two studies didn’t find such association. The association was concluded by the significant increase in the frequency of genotype and allele (A) among SCZ patients. ZNF804A gene variant at the rs1344706 was associated with the etiology of schizophrenia, with the A allele being the risk allele for the disease development.


ZNF804A Gene, rs1344706, Polymorphism, Schizophrenia, Correlation

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Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2:e141.

Liou YJ, Wang HH, Lee MT, Wang SC, Chiang HL, Chen CC, et al. Genome-wide association study of treatment refractory schizophrenia in Han Chinese. PLoS One. 2012;7:e33598.

Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry. 2003;60:1187-92.

Kendler KS, Diehl SR. The genetics of schizophrenia: a current, genetic–epidemiologic perspective. Schizophr Bull. 1993;19:261-85.

Maki P, Veijola J, Jones PB, Murray GK, Koponen H, Tienari P, et al. Predictors of schizophrenia—a review. Br Med Bull. 2005;73-4.

Chang H, Xiao X, Li M. The schizophrenia risk gene ZNF804A: clinical associations, biological mechanisms, and neuronal functions. Mol Psychiatry. 2017;22(7):944-53.

O'Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet. 2008;40:1053-5.

Riley B, Thiselton D, Maher BS, Bigdeli T, Wormley B, McMichael GO, et al. Replication of association between schizophrenia and ZNF804A in the Irish Case–Control Study of Schizophrenia sample. Mol Psychiatry. 2010;15:29-37.

Johnson MB, Kawasawa YI, Mason CE, Krsnik Z, Coppola G, Bogdanovic D, et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron. 2009;62:494-509.

Donohoe G, Morris DW, Corvin A. The psychosis susceptibility gene ZNF804A: associations, functions, and phenotypes. Schizophr Bull. 2010;36:904-9.

O’Donovan MC, Craddock NJ, Owen MJ. Genetics of psychosis; insights from views across the genome. Hum Genet. 2009;126:3-12.

Steinberg S, Mors O, Borglum AD, Gustafsson O, Werge T, Mortensen PB, et al. Expanding the range of ZNF804A variants conferring risk of psychosis. Mol Psychiatry. 2011;16:59-66.

Williams HJ, Norton N, Dwyer S, Moskvina V, Nikolov I, Carroll L, et al. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder. Mol Psychiatry. 2011;16:429-41.

Zhu M, Liu T, Zhang J, Jia S, Tang W, Luo Y. Association between rs1344706 of ZNF804A and schizophrenia: a meta-analysis. Genomics, proteomics & bioinformatics. 2014;12(6):292-6.

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100.

Anguiano LM, Camarena B, Nieto-Quinto J, de la Torre P, Laclette JP, Hirata-Hernandez H, et al. Genetic Analysis of the ZNF804A Gene in Mexican Patients with Schizophrenia, Schizoaffective Disorder and Bipolar Disorder. Research Square. 2021;829:146508.

Zhou J, Bao Q, Liang S, Guo H, Meng X, Zhang G, et al. rs1344706 polymorphism of zinc finger protein 804a (ZNF804a) gene related to the integrity of white matter fiber bundle in schizophrenics. Exp Therap Med. 2021;22(1):1-8.

de Castro-Catala M, Mora-Solano A, Kwapil TR, Cristóbal-Narváez P, Sheinbaum T, et al. The genome-wide associated candidate gene ZNF804A and psychosis-proneness: evidence of sex-modulated association. PloS One. 2017;12(9):e0185072.

Wang J, Zhao S, Shugart YY, Zhou Z, Jin C, Yuan J, et al. No association between ZNF804A rs1344706 and schizophrenia in a case-control study of Han Chinese. Neuroscience letters. 2016;618:14-8.

Mallas EJ, Carletti F, Chaddock CA, Woolley J, Picchioni MM, Shergill SS, et al. Genome-wide discovered psychosis-risk gene ZNF804A impacts on white matter microstructure in health, schizophrenia and bipolar disorder. Peer J. 2016;4:e1570.

Wei Q, Li M, Kang Z, Li L, Diao F, Zhang R, et al. ZNF804A rs1344706 is associated with cortical thickness, surface area, and cortical volume of the unmedicated first episode schizophrenia and healthy controls. Am J Med Genet B Neuropsychiatric Genetics. 2015;168(4):265-73.

Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet. 2009;373(9659):234-9.

Schwab SG, Kusumawardhani AA, Dai N, Qin W, Wildenauer MD, Agiananda F, et al. Association of rs1344706 in the ZNF804A gene with schizophrenia in a case/control sample from Indonesia. Schizophrenia Res. 2013;147(1):46-52.