Association between rs1344706 Polymorphism in the ZNF804A Gene and the Risk for Schizophrenia
Abstract
Objective: Schizophrenia is known as a severe mental disorder worldwide. Genome-wide association studies have revealed that rs1344706, located in ZNF804A, is a risk variant for schizophrenia among various populations. The current study was conducted to find correlation between rs1344706 polymorphism and schizophrenia in East of Iran.
Method: This case-control study assessed 150 schizophrenia cases as well as 150 healthy controls. The single nucleotide polymorphism (SNP) was genotyped using the Tetra-Amplification Refractory Mutation System-Polymerase Chain Reaction (Tetra-ARMS-PCR) method. Analyses based on the Chi-square test and logistic regression were calculated by SPSS.
Results: The TT, GT, and GG genotype frequencies at rs1344706 in schizophrenia cases were 48.0%, 40.0%, and 12.0%, whereas in controls, they were 49.3 %, 36.7 %, and 14.0 %, respectively. The T and G allele frequencies were 68 % and 32 % in cases and 67 % and 33 % in healthy controls. The results of logistic regression indicated that there is no association between rs1344706 alleles (P = 1.000) and genotypes (P = 0.647 for GT and P = 0.726 for GG) with susceptibility to schizophrenia.
Conclusion: Overall, there was no significant relationship between rs1344706 SNP and schizophrenia in Iran's Eastern population. However, further research focusing on more SNPs of ZNF804A and larger samples in other ethnicities is necessary to confirm these results.
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2. Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2(5):e141.
3. Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry. 2003;60(12):1187-92.
4. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421-7.
5. 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.
6. 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(9):1053-5.
7. Girgenti MJ, LoTurco JJ, Maher BJ. ZNF804a regulates expression of the schizophrenia-associated genes PRSS16, COMT, PDE4B, and DRD2. PLoS One. 2012;7(2):e32404.
8. Zhang R, Valenzuela RK, Lu S, Meng L, Guo T, Du X, et al. Is the conserved mammalian region of ZNF804A locus associated with schizophrenia? A population-based genetics analysis. Schizophr Res. 2011;133(1-3):159-64.
9. Zhou Y, Dong F, Lanz TA, Reinhart V, Li M, Liu L, et al. Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment. Mol Psychiatry. 2018;23(4):952-62.
10. Deans PJM, Raval P, Sellers KJ, Gatford NJF, Halai S, Duarte RRR, et al. Psychosis Risk Candidate ZNF804A Localizes to Synapses and Regulates Neurite Formation and Dendritic Spine Structure. Biol Psychiatry. 2017;82(1):49-61.
11. 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(1):29-37.
12. 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(4):429-41.
13. Zhang F, Chen Q, Ye T, Lipska BK, Straub RE, Vakkalanka R, et al. Evidence of sex-modulated association of ZNF804A with schizophrenia. Biol Psychiatry. 2011;69(10):914-7.
14. Tao R, Cousijn H, Jaffe AE, Burnet PW, Edwards F, Eastwood SL, et al. Expression of ZNF804A in human brain and alterations in schizophrenia, bipolar disorder, and major depressive disorder: a novel transcript fetally regulated by the psychosis risk variant rs1344706. JAMA Psychiatry. 2014;71(10):1112-20.
15. Chen J, Lin M, Hrabovsky A, Pedrosa E, Dean J, Jain S, et al. ZNF804A Transcriptional Networks in Differentiating Neurons Derived from Induced Pluripotent Stem Cells of Human Origin. PLoS One. 2015;10(4):e0124597.
16. Steinberg S, Mors O, Børglum AD, Gustafsson O, Werge T, Mortensen PB, et al. Expanding the range of ZNF804A variants conferring risk of psychosis. Mol Psychiatry. 2011;16(1):59-66.
17. Lezheiko TV, Romanov DV, Kolesina NY, Golimbet VE. Data on association of the variation (rs1344706) in the ZNF804A gene with schizophrenia and its symptoms in the Russian population. Data Brief. 2019;24:103985.
18. Zhang R, Lu SM, Qiu C, Liu XG, Gao CG, Guo TW, et al. Population-based and family-based association studies of ZNF804A locus and schizophrenia. Mol Psychiatry. 2011;16(4):360-1.
19. Chen M, Xu Z, Zhai J, Bao X, Zhang Q, Gu H, et al. Evidence of IQ-modulated association between ZNF804A gene polymorphism and cognitive function in schizophrenia patients. Neuropsychopharmacology. 2012;37(7):1572-8.
20. Li M, Luo XJ, Xiao X, Shi L, Liu XY, Yin LD, et al. Allelic differences between Han Chinese and Europeans for functional variants in ZNF804A and their association with schizophrenia. Am J Psychiatry. 2011;168(12):1318-25.
21. Li M, Shi CJ, Shi YY, Luo XJ, Zheng XB, Li ZQ, et al. ZNF804A and schizophrenia susceptibility in Asian populations. Am J Med Genet B Neuropsychiatr Genet. 2012;159b(7):794-802.
22. Yue WH, Wang HF, Sun LD, Tang FL, Liu ZH, Zhang HX, et al. Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nat Genet. 2011;43(12):1228-31.
23. Shi Y, Li Z, Xu Q, Wang T, Li T, Shen J, et al. Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nat Genet. 2011;43(12):1224-7.
24. Yang Y, Li W, Yang G, Xiao B, Wang X, Ding M, et al. Evaluation of the relationship between the ZNF804A single nucleotide polymorphism rs1344706 A/C variant and schizophrenia subtype in Han Chinese patients. Int J Psychiatry Med. 2013;45(3):269-78.
25. 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. Neurosci Lett. 2016;618:14-8.
26. 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 Neuropsychiatr Genet. 2015;168b(4):265-73.
27. 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(3):e33598.
28. Wong EH, So HC, Li M, Wang Q, Butler AW, Paul B, et al. Common variants on Xq28 conferring risk of schizophrenia in Han Chinese. Schizophr Bull. 2014;40(4):777-86.
29. Li M, Zhang H, Luo XJ, Gao L, Qi XB, Gourraud PA, et al. Meta-analysis indicates that the European GWAS-identified risk SNP rs1344706 within ZNF804A is not associated with schizophrenia in Han Chinese population. PLoS One. 2013;8(6):e65780.
30. Chung HJ, Lee JY, Deocaris CC, Min H, Kim SH, Kim MH. Mouse Homologue of the Schizophrenia Susceptibility Gene ZNF804A as a Target of Hoxc8. J Biomed Biotechnol. 2010;2010:231708.
2. Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2(5):e141.
3. Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry. 2003;60(12):1187-92.
4. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421-7.
5. 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.
6. 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(9):1053-5.
7. Girgenti MJ, LoTurco JJ, Maher BJ. ZNF804a regulates expression of the schizophrenia-associated genes PRSS16, COMT, PDE4B, and DRD2. PLoS One. 2012;7(2):e32404.
8. Zhang R, Valenzuela RK, Lu S, Meng L, Guo T, Du X, et al. Is the conserved mammalian region of ZNF804A locus associated with schizophrenia? A population-based genetics analysis. Schizophr Res. 2011;133(1-3):159-64.
9. Zhou Y, Dong F, Lanz TA, Reinhart V, Li M, Liu L, et al. Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment. Mol Psychiatry. 2018;23(4):952-62.
10. Deans PJM, Raval P, Sellers KJ, Gatford NJF, Halai S, Duarte RRR, et al. Psychosis Risk Candidate ZNF804A Localizes to Synapses and Regulates Neurite Formation and Dendritic Spine Structure. Biol Psychiatry. 2017;82(1):49-61.
11. 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(1):29-37.
12. 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(4):429-41.
13. Zhang F, Chen Q, Ye T, Lipska BK, Straub RE, Vakkalanka R, et al. Evidence of sex-modulated association of ZNF804A with schizophrenia. Biol Psychiatry. 2011;69(10):914-7.
14. Tao R, Cousijn H, Jaffe AE, Burnet PW, Edwards F, Eastwood SL, et al. Expression of ZNF804A in human brain and alterations in schizophrenia, bipolar disorder, and major depressive disorder: a novel transcript fetally regulated by the psychosis risk variant rs1344706. JAMA Psychiatry. 2014;71(10):1112-20.
15. Chen J, Lin M, Hrabovsky A, Pedrosa E, Dean J, Jain S, et al. ZNF804A Transcriptional Networks in Differentiating Neurons Derived from Induced Pluripotent Stem Cells of Human Origin. PLoS One. 2015;10(4):e0124597.
16. Steinberg S, Mors O, Børglum AD, Gustafsson O, Werge T, Mortensen PB, et al. Expanding the range of ZNF804A variants conferring risk of psychosis. Mol Psychiatry. 2011;16(1):59-66.
17. Lezheiko TV, Romanov DV, Kolesina NY, Golimbet VE. Data on association of the variation (rs1344706) in the ZNF804A gene with schizophrenia and its symptoms in the Russian population. Data Brief. 2019;24:103985.
18. Zhang R, Lu SM, Qiu C, Liu XG, Gao CG, Guo TW, et al. Population-based and family-based association studies of ZNF804A locus and schizophrenia. Mol Psychiatry. 2011;16(4):360-1.
19. Chen M, Xu Z, Zhai J, Bao X, Zhang Q, Gu H, et al. Evidence of IQ-modulated association between ZNF804A gene polymorphism and cognitive function in schizophrenia patients. Neuropsychopharmacology. 2012;37(7):1572-8.
20. Li M, Luo XJ, Xiao X, Shi L, Liu XY, Yin LD, et al. Allelic differences between Han Chinese and Europeans for functional variants in ZNF804A and their association with schizophrenia. Am J Psychiatry. 2011;168(12):1318-25.
21. Li M, Shi CJ, Shi YY, Luo XJ, Zheng XB, Li ZQ, et al. ZNF804A and schizophrenia susceptibility in Asian populations. Am J Med Genet B Neuropsychiatr Genet. 2012;159b(7):794-802.
22. Yue WH, Wang HF, Sun LD, Tang FL, Liu ZH, Zhang HX, et al. Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nat Genet. 2011;43(12):1228-31.
23. Shi Y, Li Z, Xu Q, Wang T, Li T, Shen J, et al. Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nat Genet. 2011;43(12):1224-7.
24. Yang Y, Li W, Yang G, Xiao B, Wang X, Ding M, et al. Evaluation of the relationship between the ZNF804A single nucleotide polymorphism rs1344706 A/C variant and schizophrenia subtype in Han Chinese patients. Int J Psychiatry Med. 2013;45(3):269-78.
25. 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. Neurosci Lett. 2016;618:14-8.
26. 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 Neuropsychiatr Genet. 2015;168b(4):265-73.
27. 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(3):e33598.
28. Wong EH, So HC, Li M, Wang Q, Butler AW, Paul B, et al. Common variants on Xq28 conferring risk of schizophrenia in Han Chinese. Schizophr Bull. 2014;40(4):777-86.
29. Li M, Zhang H, Luo XJ, Gao L, Qi XB, Gourraud PA, et al. Meta-analysis indicates that the European GWAS-identified risk SNP rs1344706 within ZNF804A is not associated with schizophrenia in Han Chinese population. PLoS One. 2013;8(6):e65780.
30. Chung HJ, Lee JY, Deocaris CC, Min H, Kim SH, Kim MH. Mouse Homologue of the Schizophrenia Susceptibility Gene ZNF804A as a Target of Hoxc8. J Biomed Biotechnol. 2010;2010:231708.
| Files | ||
| Issue | Vol 16 No 4 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijps.v16i4.7225 | |
| Keywords | ||
| Mental Disorder Polymorphism Schizophrenia ZNF804A Protein | ||
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How to Cite
1.
Esmaeili A, Solimani S, Karimi F, Miri-Moghaddam E. Association between rs1344706 Polymorphism in the ZNF804A Gene and the Risk for Schizophrenia. Iran J Psychiatry. 2021;16(4):383-388.
