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 Health  Vol.9 No.5 , May 2017
Are There Schizophrenia Genetic Markers and Mutations? A Systematic Review and Meta-Analyses
Abstract:
Background: Schizophrenia is a severe psychiatric disorder with a complex genetic factor determining its disease onset. Nevertheless, it is not clear in this mental disorder. Objective: To conduct a systematic review of articles regarding the genetic markers and mutations in schizophrenia. Methods: A systematic review of articles on genetic markers and mutations in schizophrenia, published from January 1, 2011, to September 7, 2015, on SCOPUS database was carried out. Search terms were “Genetic markers”, “Mutation”, and “Schizophrenia”. Results: Of the 527 retrieved studies, 31 met the eligibility criteria. Genetic polymorphism, Immune-associated genes, TCF4 and ZNF804A association with microRNA, Neuregulin gene, Chromosome 13q32 and 11p15.4, genes involved in glutamatergic via schizophrenia and brain structure, appeared to be associated with the origin of schizophrenia. Conclusion: Some studies show genes involved in several pathways leading to the disease pathogenesis such as that one related with the dopaminergic and immune system, or rare alleles. Some genes present no involvement in the etiology of this mental disorder. These findings clarify the genetic complexity of schizophrenia and affirm that together, the genes have an overall effect greater than the sum of the individual effect of each gene.
Cite this paper: Cardoso, M. , do Nascimento, T. , Bernardo, G. , Bernardo, L. , Barbosa, M. , Neto, P. , de Sousa, D. , Júnior, A. , de Lima, M. , Moreira, M. , de Sousa Gregório, D. , do Nascimento Santos, L. and Rolim Neto, M. (2017) Are There Schizophrenia Genetic Markers and Mutations? A Systematic Review and Meta-Analyses. Health, 9, 811-838. doi: 10.4236/health.2017.95058.
References

[1]   O’Donovan, M.C., Craddock, N., Norton, N., Williams, H., Peirce, T., Moskvina, V., Nikolov, I., Hamshere, M., Carroll, L., Georgieva, L., Dwyer, S., Holmans, P., Marchini, J.L., Spencer, C.C.A., Howie, B., Leung, H., Hartmann, A.M., Moller, H., Morris, D.W., Shi, Y., Feng, G., Hoffmann, P., Propping, P., Vasilescu, C., Maier, W., Rietschel, M., Zammit, S., Schumacher, J., Quinn, E.M., Schulze, T.G., Williams, N.M., Giegling, I., Iwata, N., Ikeda, M., Darvasi, A., Shifman, S., He, L., Duan, J., Sanders, A.R., Levinson, D.F., Gejman, P.V., Cichon, S., Nothen, M.M., Gill, M., Corvin, A., Rujescu, D., Kirov, G. and Owen, M.J. (2008) Identification of Loci Associated with Schizophrenia by Genome-Wide Association and Follow-Up. Nature Genetics, 40, 1053-1055.
https://doi.org/10.1038/ng.201

[2]   Zhong, N., Zhang, R., Qiu, C., Yan, H., Valenzuela, R.K., Zhang, H., Kang, W., Lu, S., Guo, T. and Ma, J. (2011) A Novel Replicated Association between FXYD6 Gene and Schizophrenia. Biochemical and Biophysical Research Communications, 405, 118-121.

[3]   Owen, M.J., Williams, H.J. and O’Donovan, M.C. (2009) Schizophrenia Genetics: Advancing on Two Fronts. Current Opinion in Genetics and Development, 19, 266-270.
https://doi.org/10.1016/j.gde.2009.02.008

[4]   Arab, A.H. and Elhawary, N.A. (2015) Association between ANKK1 (rs1800497) and LTA (rs909253) Genetic Variants and Risk of Schizophrenia. BioMed Research International, 2015, Article ID: 821827.

[5]   Gareeva, A.E. and Khusnutdinova, E.K. (2014) Polymorphism of the Glutamate Receptor Genes and Risk of Paranoid Schizophrenia in Russians and Tatars from the Republic of Bashkortostan. Molecular Biology, 48, 671-680.
https://doi.org/10.1134/s0026893314050033

[6]   Dow, D.J., Huxley-Jones, J., Hall, J.M., Francks, C., Maycox, P.R., Kew, J.N.C., Gloger, I.S., Mehta, N.A.L., Kelly, F.M., Muglia, P., Breen, G., Jugurnauth, S., Pederoso, I., St. Clair, D., Rujescu, D. and Barnes, M.R. (2011) ADAMTSL3 as a Candidate Gene for Schizophrenia: Gene Sequencing and Ultra-High Density Association Analysis by Imputation. Schizophrenia Research, 127, 28-34.
https://doi.org/10.1016/j.schres.2010.12.009

[7]   Sun, Y., Zhang, J., Yuan, Y., Yu, X., Shen, Y. and Xu, Q. (2012) Study of a Possible Role of the Monoamine Oxidase A (MAOA) Gene in Paranoid Schizophrenia Among a Chinese Population. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 159B, 104-111.
https://doi.org/10.1002/ajmg.b.32009

[8]   Yu, H., Bi, W., Liu, C., Zhao, Y., Zhang, J.F., Zhang, D. and Yue, W. (2014) Protein-Interaction-Network-Based Analysis for Genome-Wide Association Analysis of Schizophrenia in Han Chinese Population. Journal of Psychiatric Research, 50, 73-78.
https://doi.org/10.1016/j.jpsychires.2013.11.014

[9]   Cohen, J.D. and Servan-Schreiber, A. (1993) A Theory of Dopamine Function and Its Role in Cognitive Deficits in Schizophrenia. Schizophrenia Bulletin, 19, 85-104.
https://doi.org/10.1093/schbul/19.1.85

[10]   Carlsson, A., Hansson, L.O., Waters, N. and Carlsson, M.L. (1997) Neurotransmitter Aberrations in Schizophrenia: New Perspectives and Therapeutic Implications. Life Sciences, 61, 75-94.

[11]   Dai, D., Cheng, J., Zhou, K., Lv, Y., Zhuang, Q., Zheng, R., Zhang, K., Jiang, D., Gao, S. and Duan, S. (2014) Significant Association between DRD3 Gene Body Methylation. Psychiatry Research, 220, 772-777.
https://doi.org/10.1016/j.psychres.2014.08.032

[12]   Zhang, F., Liu, C., Chen, Y., Wang, L., Lu, T., Yan, H., Ruan, Y., Yue, W. and Zhang, D. (2012) No Association of Catechol-O-Methyltransferase Polymorphisms with Schizophrenia in the Han Chinese Population. Genetic Testing and Molecular Biomarkers, 16, 1138-1141.
https://doi.org/10.1089/gtmb.2012.0061

[13]   Kahler, A.K., Djurovic, S., Rimol, L.M., Brown, A.A., Jonsson, E.G., Hansen, T., Gústafsson, ó., Hall, H., Giegling, I., Muglia, P., Cichon, S., Rietschel, M., Pietila, O.P.H., Peltonen, L., Bramon, E., Collier, D., Clair, D.S., Sigurdsson, E., Petursson, H., Rujescu, D., Melle, I., Steen, V.M., Dale, A.M., Matthew, R.T., Agartz, I. and Andreassen, O.A. (2011) Candidate Gene Analysis of the Human Natural Killer-1 Carbohydrate Pathway and Perineuronal Nets in Schizophrenia: B3GAT2 Is Associated with Disease Risk and Cortical Surface Area. Biological Psychiatry, 69, 90-96.
https://doi.org/10.1016/j.biopsych.2010.07.035

[14]   Muller, N., Micheal, R., Manfred, A. and Markus, J. (1999) The Role of Immune Function in Schizophrenia: An Overview. European Archives of Psychiatry and Clinical Neuroscience, 249, S62-S68.
https://doi.org/10.1007/PL00014187

[15]   Naz, M., Riaz, M. and Saleem, M. (2011) Potential Role of Neuregulin 1 and TNF-Alpha (-308) Polymorphism in Schizophrenia Patients Visiting Hospitals in Lahore, Pakistan. Molecular Biology Reports, 38, 4709-4714.
https://doi.org/10.1007/s11033-010-0606-0

[16]   International Schizophrenia Consortium (2009) Common Polygenic Variation Contributes to Risk of Schizophrenia and Bipolar Disorder. Nature, 460, 748-752.

[17]   The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2014) Biological Insights from 108 Schizophrenia-Associated Genetic Loci. Nature, 511, 421-427.

[18]   Moselhy, H., Eapen, V., Akawi, N.A., Younis, A., Salih, B., Othman, A.R., Yousef, S., Clarke, R.A. and Ali, B. (2015) Secondary Association of PDLIM5 with Paranoid Schizophrenia in Emirati Patients. Meta Gene, 5, 135-139.

[19]   Kang, C., Zhou, L., Liu, H. and Yang, J. (2011) Association Study of the Frizzled 3 Gene with Chinese Va Schizophrenia. Neuroscience Letters, 505, 196-199.

[20]   Sullivan, P.F. (2005) The Genetics of Schizophrenia. PLoS Medicine, 2, e212.
https://doi.org/10.1371/journal.pmed.0020212

[21]   Sullivan, P., Kendler, K. and Neale, M. (2003) Schizophrenia as a complex Trait: Evidence from a Meta-Analysis of Twin Studies. Archives of General Psychiatry, 60, 1187-1192.
https://doi.org/10.1001/archpsyc.60.12.1187

[22]   Cardno, A., Marshall, E., Coid, B., Macdonald, A. and Ribchester, T. (1999) Heritability Estimates for Psychotic Disorders: The Maudsley Twin Psychosis Series. Archives of General Psychiatry, 56, 162-168.
https://doi.org/10.1001/archpsyc.56.2.162

[23]   Gadelha, A., Ota, V.K., Cano, J.P., Melaragno, M.I., Smith, M.A.C., de Jesus Mari, J., Bressan, R.A., Belangero, S.I. and Breen, G. (2012) Linkage Replication for Chromosomal Region 13q32 in Schizophrenia: Evidence from a Brazilian Pilot Study on Early Onset Schizophrenia Families. PLoS ONE, 7, e52262.
https://doi.org/10.1371/journal.pone.0052262

[24]   Jarskog, L.F., Glantz, L.A., Gilmore, J.H. and Lieberman, J.A. (2005) Apoptotic Mechanisms in the Pathophysiology of Schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29, 846-858.

[25]   Martin, M., Leffler, J. and Blom, A.M. (2012) Annexin A2 and A5 Serve as New Ligands for C1Q on Apoptotic Cells. The Journal of Biological Chemistry, 287, 33733- 33744.
https://doi.org/10.1074/jbc.M112.341339

[26]   Schoknecht, K. and Shalev, H. (2012) Blood-Brain Barrier Dysfunction in Brain Diseases: Clinical Experience. Epilepsia, 53, 7-13.
https://doi.org/10.1111/j.1528-1167.2012.03697.x

[27]   Boyajyan, A.S., Chavushyan, A.S., Zakharyan, R.V. and Mkrtchyan, G.M. (2013) Markers of Apoptotic Dysfunctions in Schizophrenia. Molecular Biology, 47, 587-591.
https://doi.org/10.1134/s002689331304002x

[28]   Lin, T., Kim, G. and Chen, J. (2003) Differential Regulation of Thrombospondin-1 and Thrombospondin-2 after Focal Cerebral Ischemia/Reperfusion. Stroke, 34, 177-186.
https://doi.org/10.1161/01.STR.0000047100.84604.BA

[29]   Tran, M. and Neary, J. (2006) Purinergic Signaling Induces Thrombospondin-1 Expression in Astrocytes. Proceedings of the National Academy of Sciences of the United States of America, 103, 9321-9326.
https://doi.org/10.1073/pnas.0603146103

[30]   Yonezawa, T., Hattori, S., Inagaki, J., Kurosaki, M., Takigawa, T., Hirohata, S., Miyoshi, T. and Ninomiya, Y. (2010) Type IV Collagen Induces Expression of Thrombospondin-1 That Is Mediated by Integrin Alpha1Beta1 in Astrocytes. Glia, 58, 755-767.

[31]   Herrick, S., Evers, D.M., Lee, J.Y., Udagawa, N. and Pak, D.T. (2010) Postsynaptic PDLIM5/Enigma Homolog Binds SPAR and Causes Dendritic Spine Shrinkage. Molecular and Cellular Neuroscience, 43, 188-200.

[32]   Bourne, J.N. and Harris, K.M. (2008) Balancing Structure and Function at Hippocampal Dendritic Spines. Annual Review of Neuroscience, 31, 47-67.
https://doi.org/10.1146/annurev.neuro.31.060407.125646

[33]   Stober, G., Saar, K. and Ruschendorf, F. (2000) Splitting Schizophrenia: Periodic Catatonia-Susceptibility Locus on Chromosome 15q15. The American Journal of Human Genetics, 67, 1201-1207.

[34]   Kury, S., Rubie, C., Moisan, J. and Stober, G. (2003) Mutation Analysis of the Zinc Transporter Gene SLC30A4 Reveals no Association with Periodic Catatonia on Chromosome 15q15. Journal of Neural Transmission, 110, 1329-1332.
https://doi.org/10.1007/s00702-003-0060-4

[35]   Moon, H., Yim, S., Lee, W., et al. (2006) Identification of DNA Copy-Number Aberrations by Array-Comparative Genomic Hybridization in Patients with Schizophrenia. Biochemical and Biophysical Research Communications, 344, 531-539.

[36]   Clarke, R.A. and Eapen, V. (2014) Balance within the Neurexin Trans-Synaptic Connexus Stabilizes Behavioral Control. Frontiers in Human Neuroscience, 8, e52.
https://doi.org/10.3389/fnhum.2014.00052

[37]   Clarke, R.A., Lee, S. and Eapen, V. (2012) Pathogenetic Model for Tourette Syndrome Delineates Overlap with Related Neurodevelopmental Disorders Including Autism. Translational Psychiatry, 2, e158.
https://doi.org/10.1038/tp.2012.75

[38]   Sharma, R.P., Grayson, D.R. and Gavin, D.P. (2008) Histone Deactylase 1 Expression Is Increased in the Prefrontal Cortex of Schizophrenia Subjects: Analysis of the National Brain Databank Microarray Collection. Schizphrena Research, 98, 111-117.
https://doi.org/10.1016/j.schres.2007.09.020

[39]   Akbarian, S., Ruehl, M.G., Bliven, E., Luiz, L.A., Peranelli, A.C., Baker, S.P., Roberts, R.C., Bunney Jr., W.E., Conley, R.C. and Jones, E.G. (2005) Chromatin Alterations Associated with Down-Regulated Metabolic Gene Expression in the Prefrontal Cortex of Subjects with Schizophrenia. Archives of General Psychiatry, 62, 829-840.
https://doi.org/10.1001/archpsyc.62.8.829

[40]   Joshi, P., Greco, T.M., Guise, A.J., Luo, Y., Yu, F., Nesvizhskii, A.I. and Cristea, I.M. (2013) The Functional Interactome Landscape of the Human Histone Deacetylase Family. Molecular Systems Biology, 9, 672.
https://doi.org/10.1038/msb.2013.26

[41]   Kebir, O., Chaumette, B., Fatjó-Vilas, M., Ambalavanan, A., Ramoz, N., Xiong, L., Mouaffak, F., Millet, B., Jaafari, N., DeLisi, L.E., Levinson, D., Joober, R., Fananás, L., Rouleau, G., Dubertret, C. and Krebs, M.O. (2014) Family-Based Association Study of Common Variants, Rare Mutation Study and Epistatic Interaction Detection in HDAC Genes in Schizophrenia. Schizophrenia Research, 160, 97-103.
https://doi.org/10.1016/j.schres.2014.09.029

[42]   Morris, J., Kandpal, G. and Ma, L. (2003) DISC1 (Disrupted-In-Schizophrenia 1) Is a Centrosome-Associated Protein That Interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: Regulation and Loss of Interaction with Mutation. Human Molecular Genetics, 12, 1591-1608.
https://doi.org/10.1093/hmg/ddg162

[43]   Ozeki, Y., Tomoda, T. and Kleiderlein, J. (2003) Disrupted-in-Schizophrenia-1 (DISC-1): Mutant Truncation Prevents Binding to NudE-Like (NUDEL) and Inhibits Neurite Outgrowth. Proceedings of the National Academy of Sciences of the United States of America, 100, 289-294.
https://doi.org/10.1073/pnas.0136913100

[44]   Cannon, T., Hennah, W. and van Erp, T. (2005) Association of DISC1/TRAX Haplo-types with Schizophrenia, Reduced Prefrontal Gray Matter, and Impaired Short- and Long-Term Memory. Archives of General Psychiatry, 62, 1205-1213.
https://doi.org/10.1001/archpsyc.62.11.1205

[45]   Cao, F., Zhang, H., Feng, J., Gao, C. and Li, S. (2013) Association Study of Three Microsatellite Polymorphisms Located in Introns 1, 8, and 9 of DISC1 with Schizophrenia in the Chinese Han Population. Genetic Testing and Molecular Biomarkers, 17, 407-411.
https://doi.org/10.1089/gtmb.2012.0438

[46]   Norlelawati, A.T., Kartini, A., Norsidah, K., Ramli, M., Tariq, A.R. and Wan Rohani, W.T. (2013) Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia. Psychiatry Investigation, 12, 103-111.
https://doi.org/10.4306/pi.2015.12.1.103

[47]   Yamada, K., Iwayama, Y., Toyota, T., Ohnishi, T., Ohba, H., Maekawa, M. and Yoshikawa, T. (2012) Association Study of the KCNJ3 Gene as a Susceptibility Candidate for Schizophrenia in the Chinese Population. Human Genetics, 131, 443-451.
https://doi.org/10.1007/s00439-011-1089-3

[48]   Okahisa, Y., Kodama, M., Takaki, M., et al. (2011) Association between the Regulator of G-Protein Signaling 9 Gene and Patients with Methamphetamine Use Disorder and Schizophrenia. Current Neuropharmacology, 9, 190-194.

[49]   Réthelyi, J.M., Bakker, S.C. and Polgár, P. (2010) Association Study of NRG1, DTNBP1, RGS4, G72/G30, and PIP5K2A with Schizophrenia and Symptom Severity in a Hungarian Sample. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153, 792-801.

[50]   De Blasi, A., Conn, P.J., Pin, J.P. and Nicoletti, F. (2001) Molecular Determinants of Metabotropic Glutamate Receptor Signaling. Trends in Pharmacological Sciences, 22, 114-120.
https://doi.org/10.1016/S0165-6147(00)01635-7

[51]   De Vries, L., Zheng, B., Fischer, T., Elenko, E. and Farquhar, M.G. (2000) The Regulator of G Protein Signaling Family. Annual Review of Pharmacology and Toxicology, 40, 235-271.

[52]   Gareeva, A.E., Zakirov, D.F., Valinurov, R.G. and Khusnutdinova, E.K. (2013) Polymorphism of RGS2 Gene as Genetic Marker of Schizophrenia Risk and Pharmacogenetic Markers of the Efficiency of Typical Neuroleptics. Molecular Biology, 47, 814-820.
https://doi.org/10.1134/S0026893313060046

[53]   Talkowski, M.E., Mansour, H., Chowdari, K.V., Wood, J., Butler, A., Varma, P.G., Prasad, S., Semwal, P., Bhatia, T., Deshpande, S., Devlin, B., Thelma, B.K. and Nimgaonkar, V.L. (2006) Novel, Replicated Associations between Dopamine D3 Receptor Gene Polymorphisms and Schizophrenia in Two Independent Samples. Biological Psychiatry, 60, 570-577.
https://doi.org/10.1016/j.biopsych.2006.04.012

[54]   Meltzer, H.Y. (1989) Clinical Studies on the Mechanism of Action of Clozapine: The Dopamine-Serotonin Hypothesis of Schizophrenia. Psychopharmacology, 99, S18-S27.

[55]   Mota, N.R., Araujo-Jnr, E.V., Paixao-Cortes, V.R., Bortolini, M.C. and Bau, C.H.D. (2012) Linking Dopamine Neurotransmission and Neurogenesis: The Evolutionary History of the NTAD (NCAM1-TTC12-ANKK1-DRD2) Gene Cluster. Genetics and Molecular Biology, 35, 912-918.
https://doi.org/10.1590/S1415-47572012000600004

[56]   Doehring, A., Hentig, N.V. and Graff, J. (2009) Genetic Variants Altering DopamineD2 Receptor Expression or Function Modulate the Risk of Opiate Addiction and the Dosage Requirements of Methadone Substitution. Pharmacogenetics and Genomics, 19, 407-414.

[57]   Jonsson, E.G., Nothen, M.M. and Neidt, H. (1999) Association between a Promoter Polymorphism in the Dopamine D2 Receptor Gene and Schizophrenia. Schizophrenia Research, 40, 31-36.
https://doi.org/10.1016/S0920-9964(99)00033-X

[58]   Shi, J., Levinson, D., Duan, J., Sanders, A. and Zheng, Y. (2009) Common Variants on Chromosome 6p22.1 Are Associated with Schizophrenia. Nature, 460, 753-757.
https://doi.org/10.1038/nature08192

[59]   Stefansson, H., Ophoff, R., Steinberg, S., Andreassen, O. and Cichon, S. (2009) Common Variants Conferring Risk of Schizophrenia. Nature, 460, 744-747.
https://doi.org/10.1038/nature08186

[60]   Ikeda, M., Aleksic, B., Kinoshita, Y., Okochi, T. and Kawashima, K. (2011) Genome-Wide Association Study of Schizophrenia in a Japanese Population. Biological Psychiatry, 69, 472-478.
https://doi.org/10.1016/j.biopsych.2010.07.010

[61]   Yue, W., Wang, H., Sun, L., Tang, F. and Liu, Z. (2011) Genome-Wide Association Study Identifies a Susceptibility Locus for Schizophrenia in Han Chinese at 11p11.2. Nature Genetics, 43, 1228-1231.
https://doi.org/10.1038/ng.979

[62]   Zhang, Y., Lu, T., Yan, H., Ruan, Y., Wang, L., Zhang, D., Yue, W. and Lu, L. (2013) Replication of Association between Schizophrenia and Chromosome 6p21-6p22.1 Polymorphisms in Chinese Han Population. PLoS ONE, 8, e56732.
https://doi.org/10.1371/journal.pone.0056732

[63]   Horton, R., Wilming, L., Rand, V., Lovering, R. and Bruford, E. (2004) Gene Map of the Extended Human MHC. Nature Reviews Genetics, 5, 889-899.
https://doi.org/10.1038/nrg1489

[64]   Shirts, B., Kim, J., Reich, S., Dickerson, F. and Yolken, R. (2007) Polymorphisms in MICB Are Associated with Human Herpes Virus Seropositivity and Schizophrenia Risk. Schizphrena Research, 94, 342-353.
https://doi.org/10.1016/j.schres.2007.04.021

[65]   Singh, B., Bera, N., De, S., Nayak, C. and Chaudhuri, T. (2011) Study of HLA Class I gene in Indian Schizophrenic Patients of Siliguri, West Benga. Psychiatry Research, 189, 215-219.
https://doi.org/10.1016/j.psychres.2011.03.010

[66]   Ripke, S., Sanders, A., Kendler, K., Levinson, D., Sklar, P., Holmans, P., Lin, D.Y., Duan, J., Ophoff, R.A., et al. (2011) Genome-Wide Association Study Identifies Five New Schizophrenia Loci. Nature Genetics, 43, 969-976.
https://doi.org/10.1038/ng.940

[67]   Steinberg, S., de Jong, S., Andreassen, O., Werge, T., Borglum, A., Mors, O., et al. (2011) Common Variants at VRK2 and TCF4 Conferring Risk of Schizophrenia. Human Molecular Genetics, 20, 4076-4081.
https://doi.org/10.1093/hmg/ddr325

[68]   Kaltschmidt, B. and Kaltschmidt, C. (2009) NF-kappaB in the Nervous System. Cold Spring Harbor Perspectives in Biology, 1, a001271.

[69]   Yamada, K., Iwayama-Shigeno, Y., Yoshida, Y., Toyota, T., Itokawa, M., Hattori, E., et al. (2004) Family-Based Association Study of Schizophrenia with 444 Markers and Analysis of a New Susceptibility Locus Mapped to 11q13.3. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 127B, 11-19.
https://doi.org/10.1002/ajmg.b.20166

[70]   Hashimoto, R., Ohi, K., Yasuda, Y., Fukumoto, M., Yamamori, H., Takahashi, H., Iwase, M., Okochi, T., Kazui, H., Saitoh, O., Tatsumi, M., Iwata, N., Ozaki, N., Kamijima, K., Kunugi, H. and Takeda, M. (2011) Variants of the RELA Gene Are Associated with Schizophrenia and Their Startle Responses. Neuropsychopharmacology, 36, 1921-1931.
https://doi.org/10.1038/npp.2011.78

[71]   Zhang, R., Yan, J.D., Valenzuela, R.K., Lu, S.M., Du, X.Y., Zhong, B., Ren, J., Zhao, S.H., Gao, C.G., Wang, L., Guo, T.W. and Ma, J. (2012) Further Evidence for the Association of Genetic Variants of ZNF804A with Schizophrenia and a Meta-Analysis for Genome-Wide Significance Variant rs1344706. Schizophrenia Research, 141, 40-47.
https://doi.org/10.1016/j.schres.2012.07.013

[72]   Ripke, S., O’Dushlaine, C., Chambert, K., Moran, J., Kahler, A., et al. (2013) Genome-Wide Association Analysis Identifies 13 New Risk Loci for Schizophrenia. Nature Genetics, 45, 1150-1159.
https://doi.org/10.1038/ng.2742

[73]   Guella, I., Sequeira, A., Rollins, B., Morgan, L., Torri, F., et al. (2013) Analysis of miR-137 Expression and rs1625579 in Dorsolateral Prefrontal Cortex. Psychiatry Research, 47, 1215-1221.
https://doi.org/10.1016/j.jpsychires.2013.05.021

[74]   Cattane, N., Minelli, A., Milanesi, E., Maj, C., Bignotti, S., Bortolomasi, M., Chiavetto, L.B. and Gennarelli, M. (2015) Altered Gene Expression in Schizophrenia: Findings from Transcriptional Signatures in Fibroblasts and Blood. PLoS ONE, 10, e0116686.
https://doi.org/10.1371/journal.pone.0116686

[75]   Hansen, T., Olsen, L., Lindow, M., Jakobsen, K.D., Ullum, H., Jonsson, E., Andreassen, O.A., Djurovic, S., Melle, L., Agartz, I., Hall, H., Timm, S., Wang, A.G. and Werge, T. (2007) Brain Expressed microRNAs Implicated in Schizophrenia Etiology. PLoS ONE, 2, e873.
https://doi.org/10.1371/journal.pone.0000873

[76]   Beveridge, N.J. and Cairns, M.J. (2012) MicroRNA Dysregulation in Schizophrenia. Neurobiology of Disease, 46, 263-271.
https://doi.org/10.1016/j.nbd.2011.12.029

[77]   Joshi, D., Fullerton, J.M. and Weickert, C.S. (2014) Elevated ErbB4 mRNA Is Related to Interneuron Deficit in Prefrontal Cortex in Schizophrenia. Journal of Psychiatric Research, 53, 125-132.
https://doi.org/10.1016/j.jpsychires.2014.02.014

[78]   Norton, N., Moskvina, V., Morris, D., Bray, N., Zammit, S., Williams, N., et al. (2006) Evidence That Interaction between Neuregulin 1 and Its Receptor erbB4 Increases Susceptibility to Schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 141B, 96-101.
https://doi.org/10.1002/ajmg.b.30236

[79]   Silberberg, G., Darvasi, A., Pinkas-Kramarski, R. and Navon, R. (2006) The Involvement of ErbB4 with Schizophrenia: Association and Expression Studies. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 141B, 142-148.
https://doi.org/10.1002/ajmg.b.30275

[80]   Stefansson, H. (2002) Neuregulin 1 and Susceptibility to Schizophrenia. American Journal of Human Genetics, 71, 877-892.
https://doi.org/10.1086/342734

[81]   Fazzari, P., Paternain, A., Valiente, M., Pla, R., Lujan, R., Lloyd, K., et al. (2010) Control of Cortical GABA Circuitry Development by Nrg1 and ErbB4 Signalling. Nature, 464, 1376-1380.

[82]   Krivosheya, D., Tapia, L., Levinson, J., Huang, K., Kang, Y., Hines, R., et al. (2008) ErbB4-Neuregulin Signaling Modulates Synapse Development and Dendritic Arborization through Distinct Mechanisms. The Journal of Biological Chemistry, 283, 32944-32956.
https://doi.org/10.1074/jbc.M800073200

[83]   Weickert, C., Tiwari, Y., Schofield, P., Mowry, B. and Fullerton, J. (2012) Schizophrenia-Associated HapICE Haplotype Is Associated with Increased NRG1 Type III Expression and High Nucleotide Diversity. Translational Psychiatry, 2, e104.
https://doi.org/10.1038/tp.2012.25

[84]   Chong, V., Thompson, M., Beltaifa, S., Webster, M., Law, A. and Weickert, C. (2008) Elevated Neuregulin-1 and ErbB4 Protein in the Prefrontal Cortex of Schizophrenic Patients. Schizophrenia Research, 100, 270-280.
https://doi.org/10.1016/j.schres.2007.12.474

[85]   Chen, P.L., Avramopoulos, D., Lasseter, V.K., McGrath, J.A., Fallin, M.D., Liang, K.Y., Nestadt, G., Feng, N., Steel, G., Cutting, A.S., Wolyniec, P., Pulver, A.E. and Valle, D. (2009) Fine Mapping on Chromosome 10q22-q23 Implicates Neuregulin 3 in Schizophrenia. American Journal of Human Genetics, 84, 21-34.
https://doi.org/10.1016/j.ajhg.2008.12.005

[86]   Ryu, S., Won, H.H., Oh, S., Jong-Won, K., Park, T., Cho, E.Y., Cho, Y., Park, D.Y., Lee, Y.S., Kwon, J.S. and Hong, K.S. (2013) Genome-Wide Linkage Scan of Quantitative Traits representing Symptom Dimensions in Multiplex Schizophrenia Families. Psychiatry Research, 210, 756-760.
https://doi.org/10.1016/j.psychres.2013.08.015

[87]   Blouin, J., Dombroski, B., Nath, S., Lasseter, V., Wolyniec, P., et al. (1998) Schizophrenia Susceptibility Loci on Chromosomes 13q32 and 8p21. Nature Genetics, 20, 70-73.

[88]   Lander, E. and Kruglyak, L. (1995) Genetic Dissection of Complex Traits: Guidelines for Interpreting and Reporting Linkage Results. Nature Genetics, 11, 241-247.
https://doi.org/10.1038/ng1195-241

[89]   Brzustowicz, L., Honer, W., Chow, E., Little, D. and Hogan, J. (1999) Linkage of Familial Schizophrenia to Chromosome 13q32. The American Journal of Human Genetics, 65, 1096-1103.
https://doi.org/10.1086/302579

[90]   Brzustowicz, L., Hodgkinson, K., Chow, E., Honer, W. and Bassett, A. (2000) Location of a Major Susceptibility Locus for Familial Schizophrenia on Chromosome 1q21-q22. Science, 288, 678-682.
https://doi.org/10.1126/science.288.5466.678

[91]   Huang, J., Perlis, R., Lee, P., Rush, A., Fava, M., et al. (2010) Cross-Disorder Genomewide Analysis of Schizophrenia, Bipolar Disorder, and Depression. The American Journal of Psychiatry, 167, 1254-1263.
https://doi.org/10.1176/appi.ajp.2010.09091335

[92]   Liu, X., Paterson, A. and Szatmari, P., The Autism Genome Project Consortium (2008) Genome-Wide Linkage Analyses of Quantitative and Categorical Autism Subphenotypes. Biological Psychiatry, 64, 561-570.
https://doi.org/10.1016/j.biopsych.2008.05.023

[93]   Gornick, M., Addington, A., Shaw, P., Bobb, A. and Sharp, W. (2007) Association of the Dopamine Receptor D4 (DRD4) Gene 7-Repeat Allele with Children with Attention-Deficit/Hyperactivity Disorder (ADHD): An Update. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 144B, 379-382.
https://doi.org/10.1002/ajmg.b.30460

[94]   Gareeva, A.E., Zakirovb, D.F. and Khusnutdinovaa, E.K. (2013) Association Polymorphic Variants of GRIN2B Gene with Paranoid Schizophrenia and Response to Typical Neuroleptics in Russians and Tatars from Bashkortostan Republic. Russian Journal of Genetics, 49, 962-968.
https://doi.org/10.1134/S1022795413080024

[95]   Coyle, J.T. (2006) Glutamate and Schizophrenia: Beyond the Dopamine Hypothesis. Cellular and Molecular Neurobiology, 26, 363-382.
https://doi.org/10.1007/s10571-006-9062-8

[96]   Javitt, D.C. (2010) Glutamatergic Theories of Schizophrenia. The Israel Journal of Psychiatry and Related Sciences, 47, 4-16.

[97]   Clinton, S.M. and Meador-Woodruff, J.H. (2004) Thalamic Dysfunction in Schizophrenia: Neurochemical, Neuropathological and in Vivo Imaging Abnormalities. Schizophrenia Research, 69, 237-253.
https://doi.org/10.1016/j.schres.2003.09.017

[98]   Pelov, I., Teltsh, O., Greenbaum, L., Rigbi, A., Kanyas-Sarner, K., Lerer, B., Lombroso, P. and Kohn, Y. (2012) Involvement of PTPN5, the Gene Encoding the Striatal-Enriched Protein Tyrosine Phosphatase, in Schizophrenia and Cognition. Psychiatric Genetics, 22, 168-176.
https://doi.org/10.1097/YPG.0b013e3283518586

[99]   Martucci, L., Wong, A.H., De Luca, V., et al. (2006) N-Methyl-D-Aspartate Receptor NR2B Subunit Gene GRIN2B in Schizophrenia and Bipolar Disorder: Polymorphisms and mRNA Levels. Schizophrenia Research, 84, 214-221.
https://doi.org/10.1016/j.schres.2006.02.001

[100]   Numakawa, T., Yagasaki, Y., Ishimoto, T., Okada, T., Suzuki, T., Iwata, N., et al. (2004) Evidence of Novel Neuronal Functions of Dysbindin, a Susceptibility Gene for Schizophrenia. Human Molecular Genetics, 13, 2699-2708.
https://doi.org/10.1093/hmg/ddh280

[101]   Talbot, K., Cho, D., Ong, W., Benson, M., Han, L., Kazi, H., et al. (2006) Dysbindin-1 Is a Synaptic and Microtubular Protein That Binds Brain Snapin. Human Molecular Genetics, 15, 3041-3054.
https://doi.org/10.1093/hmg/ddl246

[102]   Cerasa, A., Quattrone, A., Gioia, M.C., Tarantino, P., Annesi, G., Assogna, F., Caltagirone, C., De Luca, V. and Spalletta, G. (2011) Dysbindin C-A-T Haplotype Is Associated with Thicker Medial Orbitofrontal Cortex in Healthy Population. NeuroImage, 55, 508-513.

[103]   Barbon, A. and Barlati, S. (2000) Genomic Organization, Proposed Alternative Splicing Mechanisms, and RNA Editing Structure of GRIK1. Cytogenetics and Cell Genetics, 88, 236-239.
https://doi.org/10.1159/000015558

[104]   Hirata, Y., Zai, C., Souza, R.P., Lieberman, J.A., Meltzer, H.Y. and Kennedy, J.L. (2012) Association Study of GRIK1 Gene Polymorphisms in Schizophrenia: Case-Control and Family-Based Studies. Human Psychopharmacology, 27, 345-351.
https://doi.org/10.1002/hup.2233

[105]   Bah, J., Quach, R., Ebstein, P., Segman, R.H., Melke, J., Jamain, S., Rietschel, M., Modai, I., Kanas, K., Karni, O., Lerer, B., Gourion, D., Krebs, M.O., Etain, B., Schürhoff, F., Szoke, A., Leboyer, M. and Bourgeron, T. (2004) Maternal Transmission Disequilibrium of the Glutamate Receptor GRIK2 in Schizophrenia. NeuroReport, 15, 1987-1991.

[106]   Ekholm, J.M., Kieseppa, T., Hiekkalinna, T., et al. (2003) Evidence of Susceptibility Loci on 4q32 and 16p12 for Bipolar Disorder. Human Molecular Genetics, 12, 1907-1915.
https://doi.org/10.1093/hmg/ddg199

[107]   Geering, K. (2006) FXYD Proteins: New Regulators of Na-K-ATPase. American Journal of Physiology-Renal Physiology, 290, F241-F250.
https://doi.org/10.1152/ajprenal.00126.2005

[108]   Rose, E.M., Koo, J.C., Antflick, J.E., Ahmed, S.M., Angers, S. and Hampson, D.R. (2009) Glutamate Transporter Coupling to Na, K-ATPase. Journal of Neuroscienc, 29, 8143-8155.
https://doi.org/10.1523/JNEUROSCI.1081-09.2009

[109]   Barch, D. (2005) The Cognitive Neuroscience of Schizophrenia. AAnnual Review of Clinical Psychology, 1, 321-353.
https://doi.org/10.1146/annurev.clinpsy.1.102803.143959

[110]   Karlsgodt, K., Sun, D., Jimenez, A., Lutkenhoff, E., Willhite, R., van Erp, T. and Cannon, T. (2008) Developmental Disruptions in Neural Connectivity in the Pathophysiology of Schizophrenia. Development and Psychopathology, 20, 1297-1327.
https://doi.org/10.1017/S095457940800062X

[111]   Pantazopoulos, H., Woo, T.U., Lim, M.P., Lange, N. and Berretta, S. (2010) Extracellular Matrix-Glial Abnormalities in the Amygdala and Entorhinal Cortex of Subjects Diagnosed with Schizophrenia. Archives of General Psychiatry, 67, 155-166.

[112]   Rimol, L., Hartberg, C., Nesvag, R., Fennema-Notestine, C., Hagler, D.J., Pung, C., et al. (2010) Cortical Thickness and Subcortical Volumes in Schizophrenia and Bipolar Disorder. Biological Psychiatry, 68, 41-50.
https://doi.org/10.1016/j.biopsych.2010.03.036

[113]   Kleene, R. and Schachner, M. (2004) Glycans and Neural Cell Interactions. Nature Reviews Neuroscience, 5, 195-208.
https://doi.org/10.1038/nrn1349

[114]   Morita, I., Kizuka, Y., Kakuda, S. and Oka, S. (2008) Expression and Function of the HNK-1 Carbohydrate. The Journal of Biochemistry, 143, 719-724.
https://doi.org/10.1093/jb/mvm221

[115]   Weedon, M.N., Lango, J., Lindgren, C.M., Wallace, C., Evans, D.M., Mangino, M., Freathy, R.M., Perry, J.R., Stevens, S., Hall, A.S., Samani, N.J., Shields, B., Prokopenko, I., Farrall, M., Dominiczak, A., Diabetes Genetics Initiative, Wellcome Trust Case Control Consortium, Johnson, T., Bergmann, S., Beckmann, J.S., Vollenweider, P., Waterworth, D.M., Mooser, V., Palmer, C.N., Morris, A.D., Ouwehand, W.H., Cambridge GEM Consortium, Zhao, J.H., Li, S., Loos, R.J., Barroso, I., Deloukas, P., Sandhu, M.S., Wheeler, E., Soranzo, N., Inouye, M., Wareham, N.J., Caulfield, M., Munroe, P.B., Hattersley, A.T., McCarthy, M.I., Frayling, T.M., et al. (2008) Genome-Wide Association Analysis Identifies 20 Loci That Influence Adult Height. Nature Genetics, 40, 575-583.

[116]   Williams, N.M., Preece, A., Morris, D.W., Spurlock, G., Bray, N.J., Stephens, M., et al. (2004) Identification in 2 Independent Samples of a Novel Schizophrenia Risk Haplotype of the Dystrobrevin Binding Protein Gene (DTNBP1). Archives of General Psychiatry, 61, 336-344.
https://doi.org/10.1001/archpsyc.61.4.336

[117]   Bray, N.J., Preece, A., Williams, N.M., Moskvina, V., Buckland, P.R., Owen, M.J. and O’Donovan, M.C. (2005) Haplotypes at the Dystrobrevin Binding Protein 1 (DTNBP1) Gene Locus Mediate Risk for Schizophrenia through Reduced DTNBP1 Expression. Human Molecular Genetics, 14, 1947-1954.
https://doi.org/10.1093/hmg/ddi199

[118]   Donohoe, G., Morris, D., Clarke, S., McGhee, K., Schwaiger, S., Nangle, J.M., Garavan, H., Robertson, I.H., Gill, M. and Corvin, A. (2007) Variance in Neurocognitive Performance Is Associated with Dysbindin-1 in Schizophrenia: A Preliminary Study. Neuropsychologia, 45, 454-458.

[119]   Donohoe, G., Frodl, T., Morris, D., Spoletini, I., Cannon, D.M., Cherubini, A., Caltagirone, C., Bossù, P., McDonald, C., Gill, M., Corvin, A.P. and Spalletta, G. (2010) Reduced Occipital and Prefrontal Brain Volumes in Dysbindin-Associated Schizophrenia. Neuropsychopharmacology, 35, 368-373.
https://doi.org/10.1038/npp.2009.140

[120]   Saito, A., Fujikura-Ouchi, Y., Ito, C., Matsuoka, H., Shimoda, K. and Akiyama, K. (2011) An Association Study on Polymorphisms in the PEA15, ENTPD4, and GAS2L1 Genes and Schizophrenia. Psychiatry Research, 185, 9-15.
https://doi.org/10.1016/j.psychres.2009.09.018

[121]   Lewis, C., Levinson, D., Wise, L., et al. (2003) Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia. American Journal of Human Genetics, 73, 34-48.
https://doi.org/10.1086/376549

 
 
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