Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016;388:86–97.

PubMed  PubMed Central  Article  Google Scholar 

Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382:1575–86.

PubMed  Article  Google Scholar 

Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, et al. Global epidemiology and burden of schizophrenia: findings from the global burden of disease study 2016. Schizophr Bull. 2018;44:1195–203.

PubMed  PubMed Central  Article  Google Scholar 

American Psychiatric Association. Diagnostic and statistical manual of mental disorders 5th ed. (DSM-5). Arlington: American Psychiatric Publishing; 2013.

Zhuo C, Hou W, Li G, Mao F, Li S, Lin X, et al. The genomics of schizophrenia: shortcomings and solutions. Prog Neuropsychopharmacol Biol Psychiatry. 2019;93:71–76.

CAS  PubMed  Article  Google Scholar 

Kimura H, Mori D, Aleksic B, Ozaki N. Elucidation of molecular pathogenesis and drug development for psychiatric disorders from rare disease-susceptibility variants. Neurosci Res. 2021;170:24–31.

CAS  PubMed  Article  Google Scholar 

Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait. Arch Gen Psychiatry. 2003;60:1187.

PubMed  Article  Google Scholar 

Hilker R, Helenius D, Fagerlund B, Skytthe A, Christensen K, Werge TM, et al. Heritability of schizophrenia and schizophrenia spectrum based on the nationwide danish twin register. Biol Psychiatry. 2018;83:492–98.

PubMed  Article  Google Scholar 

Stessman HA, Bernier R, Eichler EE. A genotype-first approach to defining the subtypes of a complex disease. Cell. 2014;156:872–77.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Nakatochi M, Kushima I, Ozaki N. Implications of germline copy-number variations in psychiatric disorders: review of large-scale genetic studies. J Hum Genet. 2021;66:25–37.

PubMed  Article  Google Scholar 

Zarrei M, MacDonald JR, Merico D, Scherer SW. A copy number variation map of the human genome. Nat Rev Genet. 2015;16:172–83.

CAS  PubMed  Article  Google Scholar 

Stankiewicz P, Lupski JR. Structural variation in the human genome and its role in disease. Annu Rev Med. 2010;61:437–55.

CAS  PubMed  Article  Google Scholar 

Rees E, Walters JTR, Georgieva L, Isles AR, Chambert KD, Richards AL, et al. Analysis of copy number variations at 15 schizophrenia-associated loci. Brit J Psychiat. 2014;204:108–14.

PubMed  Article  Google Scholar 

Marshall CR, Howrigan DP, Merico D, Thiruvahindrapuram B, Wu W, Greer DS, et al. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects. Nat Genet. 2017;49:27–35.

CAS  PubMed  Article  Google Scholar 

Kushima I, Aleksic B, Nakatochi M, Shimamura T, Shiino T, Yoshimi A, et al. High-resolution copy number variation analysis of schizophrenia in Japan. Mol Psychiatry. 2017;22:430–40.

CAS  PubMed  Article  Google Scholar 

McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, et al. 22q11.2 deletion syndrome. Nat Rev Dis Prim. 2015;1:15071.

PubMed  Article  Google Scholar 

Fiksinski AM, Schneider M, Murphy CM, Armando M, Vicari S, Canyelles JM, et al. Understanding the pediatric psychiatric phenotype of 22q11.2 deletion syndrome. Am J Med Genet A. 2018;176:2182–91.

PubMed  PubMed Central  Article  Google Scholar 

Schneider M, Debbane M, Bassett AS, Chow EW, Fung WL, van den Bree M, et al. Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome. Am J Psychiatry. 2014;171:627–39.

PubMed  PubMed Central  Article  Google Scholar 

Jonas RK, Montojo CA, Bearden CE. The 22q11.2 deletion syndrome as a window into complex neuropsychiatric disorders over the lifespan. Biol Psychiatry. 2014;75:351–60.

CAS  PubMed  Article  Google Scholar 

Mok KY, Sheerin U, Simon-Sanchez J, Salaka A, Chester L, Escott-Price V, et al. Deletions at 22q11.2 in idiopathic Parkinson’s disease: a combined analysis of genome-wide association data. Lancet Neurol. 2016;15:585–96.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kushima I, Aleksic B, Nakatochi M, Shimamura T, Okada T, Uno Y, et al. Comparative analyses of copy-number variation in autism spectrum disorder and schizophrenia reveal etiological overlap and biological insights. Cell Rep. 2018;24:2838–56.

CAS  PubMed  Article  Google Scholar 

Hayashi Y, Kushima I, Aleksic B, Senaha T, Ozaki N. Variable psychiatric manifestations in patients with 16p11.2 duplication: a case series of 4 patients. Psychiatry Clin Neurosci. 2021;76:86–8.

Article  CAS  Google Scholar 

Kato H, Kushima I, Mori D, Yoshimi A, Aleksic B, Nawa Y, et al. Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder. Transl Psychiatry. 2020;10:421.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kimura H, Kushima I, Yohimi A, Aleksic B, Ozaki N. Copy number variant in the region of adenosine kinase (ADK) and its possible contribution to schizophrenia susceptibility. Int J Neuropsychopharmacol. 2018;21:405–09.

CAS  PubMed  Article  Google Scholar 

Sobue A, Kushima I, Nagai T, Shan W, Kohno T, Aleksic B, et al. Genetic and animal model analyses reveal the pathogenic role of a novel deletion of RELN in schizophrenia. Sci Rep. 2018;8:13046.

PubMed  PubMed Central  Article  CAS  Google Scholar 

Saito R, Koebis M, Nagai T, Shimizu K, Liao J, Wulaer B, et al. Comprehensive analysis of a novel mouse model of the 22q11.2 deletion syndrome: a model with the most common 3.0-Mb deletion at the human 22q11.2 locus. Transl Psychiatry. 2020;10:35.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Arioka Y, Shishido E, Kushima I, Suzuki T, Saito R, Aiba A, et al. Chromosome 22q11.2 deletion causes PERK-dependent vulnerability in dopaminergic neurons. EBioMedicine. 2021;63:103138.

CAS  PubMed  Article  Google Scholar 

Sekiguchi M, Sobue A, Kushima I, Wang C, Arioka Y, Kato H, et al. ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk. Transl Psychiatry. 2020;10:247.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Sanders SJ, Neale BM, Huang H, Werling DM, An JY, Dong S, et al. Whole genome sequencing in psychiatric disorders: the WGSPD consortium. Nat Neurosci. 2017;20:1661–68.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kimura H, Fujita Y, Kawabata T, Ishizuka K, Wang C, Iwayama Y, et al. A novel rare variant R292H in RTN4R affects growth cone formation and possibly contributes to schizophrenia susceptibility. Transl Psychiatry. 2017;7:e1214.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kimura H, Tsuboi D, Wang C, Kushima I, Koide T, Ikeda M, et al. Identification of rare, single-nucleotide mutations in NDE1 and their contributions to schizophrenia susceptibility. Schizophr Bull. 2015;41:744–53.

PubMed  Article  Google Scholar 

Ishizuka K, Fujita Y, Kawabata T, Kimura H, Iwayama Y, Inada T, et al. Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders. Transl Psychiatry. 2017;7:e1184.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Ishizuka K, Yoshida T, Kawabata T, Imai A, Mori H, Kimura H, et al. Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia. J Neurodev Disord. 2020;12:25.

PubMed  PubMed Central  Article  Google Scholar 

Girard SL, Gauthier J, Noreau A, Xiong L, Zhou S, Jouan L, et al. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet. 2011;43:860–3.

CAS  PubMed  Article  Google Scholar 

Xu B, Ionita-Laza I, Roos JL, Boone B, Woodrick S, Sun Y, et al. De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nat Genet. 2012;44:1365–9.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P. et al. De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014;506:179–84.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Uno Y, Coyle JT. Glutamate hypothesis in schizophrenia. Psychiatry Clin Neurosci. 2019;73:204–15.

PubMed  Article  Google Scholar 

Darnell JC, Van Driesche SJ, Zhang C, Hung KY, Mele A, Fraser CE. et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell. 2011;146:247–61.

CAS  PubMed  PubMed Central  Article  Google Scholar