Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Transcriptome sequencing and genome-wide association analyses reveal lysosomal function and actin cytoskeleton remodeling in schizophrenia and bipolar disorder

Molecular Psychiatry volume 20, pages 563–572 (2015)Cite this article

Subjects

Abstract

Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental disorders with high heritability. Clinicians have long noticed the similarities of clinic symptoms between these disorders. In recent years, accumulating evidence indicates some shared genetic liabilities. However, what is shared remains elusive. In this study, we conducted whole transcriptome analysis of post-mortem brain tissues (cingulate cortex) from SCZ, BPD and control subjects, and identified differentially expressed genes in these disorders. We found 105 and 153 genes differentially expressed in SCZ and BPD, respectively. By comparing the t-test scores, we found that many of the genes differentially expressed in SCZ and BPD are concordant in their expression level (q⩽0.01, 53 genes; q⩽0.05, 213 genes; q⩽0.1, 885 genes). Using genome-wide association data from the Psychiatric Genomics Consortium, we found that these differentially and concordantly expressed genes were enriched in association signals for both SCZ (P<10−7) and BPD (P=0.029). To our knowledge, this is the first time that a substantially large number of genes show concordant expression and association for both SCZ and BPD. Pathway analyses of these genes indicated that they are involved in the lysosome, Fc gamma receptor-mediated phagocytosis, regulation of actin cytoskeleton pathways, along with several cancer pathways. Functional analyses of these genes revealed an interconnected pathway network centered on lysosomal function and the regulation of actin cytoskeleton. These pathways and their interacting network were principally confirmed by an independent transcriptome sequencing data set of the hippocampus. Dysregulation of lysosomal function and cytoskeleton remodeling has direct impacts on endocytosis, phagocytosis, exocytosis, vesicle trafficking, neuronal maturation and migration, neurite outgrowth and synaptic density and plasticity, and different aspects of these processes have been implicated in SCZ and BPD.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

References

  1. Sheng G, Demers M, Subburaju S, Benes FM . Differences in the circuitry-based association of copy numbers and gene expression between the hippocampi of patients with schizophrenia and the hippocampi of patients with bipolar disorder. Arch Gen Psychiatry 2012; 69: 550–561.

    Article  CAS  PubMed  Google Scholar 

  2. Karege F, Meary A, Perroud N, Jamain S, Leboyer M, Ballmann E, et al. Genetic overlap between schizophrenia and bipolar disorder: a study with AKT1 gene variants and clinical phenotypes. Schizophr Res 2012; 135: 8–14.

    Article  PubMed  Google Scholar 

  3. Williams HJ, Craddock N, Russo G, Hamshere ML, Moskvina V, Dwyer S, et al. Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-traditional diagnostic boundaries. Hum Mol Genet 2011; 20: 387–391.

    Article  CAS  PubMed  Google Scholar 

  4. Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460: 748–752.

    CAS  PubMed  Google Scholar 

  5. Kubicki M, Westin CF, Nestor PG, Wible CG, Frumin M, Maier SE, et al. Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study. Biol Psychiatry 2003; 54: 1171–1180.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Yucel M, Pantelis C, Stuart GW, Wood SJ, Maruff P, Velakoulis D, et al. Anterior cingulate activation during Stroop task performance: a PET to MRI coregistration study of individual patients with schizophrenia. Am J Psychiatry 2002; 159: 251–254.

    Article  PubMed  Google Scholar 

  7. Li R, Li Y, Kristiansen K, Wang J . SOAP: short oligonucleotide alignment program. Bioinformatics 2008; 24: 713–714.

    Article  CAS  PubMed  Google Scholar 

  8. Li R, Yu C, Li Y, Lam TW, Yiu SM, Kristiansen K, et al. SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 2009; 25: 1966–1967.

    Article  CAS  PubMed  Google Scholar 

  9. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B . Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 2008; 5: 621–628.

    Article  CAS  PubMed  Google Scholar 

  10. Yi X, Liang Y, Huerta-Sanchez E, Jin X, Cuo ZX, Pool JE, et al. Sequencing of 50 human exomes reveals adaptation to high altitude. Science 2010; 329: 75–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ripke S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA, et al. Genome- wide association study identifies five new schizophrenia loci. Nat Genet 2011; 43: 969–976.

    CAS  Google Scholar 

  12. Sklar P, Ripke S, Scott LJ, Andreassen OA, Cichon S, Craddock N, et al. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 2011; 43: 977–983.

    Article  CAS  PubMed Central  Google Scholar 

  13. Liu JZ, McRae AF, Nyholt DR, Medland SE, Wray NR, Brown KM, et al. A versatile gene-based test for genome-wide association studies. Am J Hum Genet 2010; 87: 139–145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Storey JD, Tibshirani R . Statistical significance for genomewide studies. Proc Natl Acad Sci USA 2003; 100: 9440–9445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ho D, Imai K, King G, Stuart E . Matching as nonparametric preprocessing for reducing model dependence in parametric causal inference. Polit Anal 2007; 15: 199–236.

    Article  Google Scholar 

  16. Zhang B, Kirov S, Snoddy J . WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res 2005; 33: W741–W748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jia P, Liu Y, Zhao Z . Integrative pathway analysis of genome-wide association studies and gene expression data in prostate cancer. BMC Syst Biol 2012; 6 (Suppl 3): S13.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Benjamini Y, Hochberg Y . Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc Ser B 1995; 57: 289–300.

    Google Scholar 

  19. Huang Y, Li S . Detection of characteristic sub pathway network for angiogenesis based on the comprehensive pathway network. BMC Bioinform 2010; 11 (Suppl 1): S32.

    Article  Google Scholar 

  20. Wu J, Vallenius T, Ovaska K, Westermarck J, Makela TP, Hautaniemi S . Integrated network analysis platform for protein–protein interactions. Nat Methods 2009; 6: 75–77.

    Article  CAS  PubMed  Google Scholar 

  21. Roig B, Franco-Pons N, Martorell L, Tomas J, Vogel WF, Vilella E . Expression of the tyrosine kinase discoidin domain receptor 1 (DDR1) in human central nervous system myelin. Brain Res 2010; 1336: 22–29.

    Article  CAS  PubMed  Google Scholar 

  22. Roig B, Virgos C, Franco N, Martorell L, Valero J, Costas J, et al. The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia. Mol Psychiatry 2007; 12: 833–841.

    Article  CAS  PubMed  Google Scholar 

  23. Athanasiu L, Mattingsdal M, Melle I, Inderhaug E, Lien T, Agartz I, et al. Intron 12 in NTRK3 is associated with bipolar disorder. Psychiatry Res 2011; 185: 358–362.

    Article  CAS  PubMed  Google Scholar 

  24. Otnaess MK, Djurovic S, Rimol LM, Kulle B, Kahler AK, Jonsson EG, et al. Evidence for a possible association of neurotrophin receptor (NTRK-3) gene polymorphisms with hippocampal function and schizophrenia. Neurobiol Dis 2009; 34: 518–524.

    Article  CAS  PubMed  Google Scholar 

  25. Kwon E, Wang W, Tsai LH . Validation of schizophrenia-associated genes CSMD1, C10orf26, CACNA1C and TCF4 as miR-137 targets. Mol Psychiatry 2013; 18: 11–12.

    Article  CAS  PubMed  Google Scholar 

  26. Kim AH, Parker EK, Williamson V, McMichael GO, Fanous AH, Vladimirov VI . Experimental validation of candidate schizophrenia gene ZNF804A as target for hsa-miR-137. Schizophr Res 2012; 141: 60–64.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Qualmann B, Kessels MM . Endocytosis and the cytoskeleton. Int Rev Cytol 2002; 220: 93–144.

    Article  CAS  PubMed  Google Scholar 

  28. Kim S, Webster MJ . Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders. Mol Psychiatry 2010; 15: 326–336.

    Article  CAS  PubMed  Google Scholar 

  29. Niehrs C . The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol 2012; 13: 767–779.

    Article  CAS  PubMed  Google Scholar 

  30. van der Sluijs P, Hoogenraad CC . New insights in endosomal dynamics and AMPA receptor trafficking. Semin Cell Dev Biol 2011; 22: 499–505.

    Article  CAS  PubMed  Google Scholar 

  31. Scita G, Di Fiore PP . The endocytic matrix. Nature 2010; 463: 464–473.

    Article  CAS  PubMed  Google Scholar 

  32. Lipinski MM, Zheng B, Lu T, Yan Z, Py BF, Ng A, et al. Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer's disease. Proc Natl Acad Sci USA 2010; 107: 14164–14169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pimplikar SW, Nixon RA, Robakis NK, Shen J, Tsai LH . Amyloid-independent mechanisms in Alzheimer's disease pathogenesis. J Neurosci 2010; 30: 14946–14954.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Koga H, Martinez-Vicente M, Arias E, Kaushik S, Sulzer D, Cuervo AM . Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease. J Neurosci 2011; 31: 18492–18505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Martinez-Vicente M, Talloczy Z, Wong E, Tang G, Koga H, Kaushik S, et al. Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease. Nat Neurosci 2010; 13: 567–576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Auer M, Hausott B, Klimaschewski L . Rho GTPases as regulators of morphological neuroplasticity. Ann Anat 2011; 193: 259–266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. de C I . Functions of Rac GTPases during neuronal development. Dev Neurosci 2008; 30: 47–58.

    Article  Google Scholar 

  38. Deo AJ, Goldszer IM, Li S, Dibitetto JV, Henteleff R, Sampson A, et al. PAK1 Protein Expression in the Auditory Cortex of Schizophrenia Subjects. PLoS One 2013; 8: e59458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bellenchi GC, Gurniak CB, Perlas E, Middei S, Ammassari-Teule M, Witke W . N-cofilin is associated with neuronal migration disorders and cell cycle control in the cerebral cortex. Genes Dev 2007; 21: 2347–2357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kreis P, Barnier JV . PAK signalling in neuronal physiology. Cell Signal 2009; 21: 384–393.

    Article  CAS  PubMed  Google Scholar 

  41. Lundquist EA . Rac proteins and the control of axon development. Curr Opin Neurobiol 2003; 13: 384–390.

    Article  CAS  PubMed  Google Scholar 

  42. Rubio MD, Haroutunian V, Meador-Woodruff JH . Abnormalities of the Duo/Ras-related C3 botulinum toxin substrate 1/p21-activated kinase 1 pathway drive myosin light chain phosphorylation in frontal cortex in schizophrenia. Biol Psychiatry 2012; 71: 906–914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ide M, Lewis DA . Altered cortical CDC42 signaling pathways in schizophrenia: implications for dendritic spine deficits. Biol Psychiatry 2010; 68: 25–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mah S, Nelson MR, DeLisi LE, Reneland RH, Markward N, James MR, et al. Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia. Mol Psychiatry 2006; 11: 471–478.

    Article  CAS  PubMed  Google Scholar 

  45. Rujescu D, Meisenzahl EM, Krejcova S, Giegling I, Zetzsche T, Reiser M, et al. Plexin B3 is genetically associated with verbal performance and white matter volume in human brain. Mol Psychiatry 2007; 12: 190–194.

    Article  CAS  PubMed  Google Scholar 

  46. Eastwood SL, Law AJ, Everall IP, Harrison PJ . The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its synaptic pathology. Mol Psychiatry 2003; 8: 148–155.

    Article  CAS  PubMed  Google Scholar 

  47. Hattori T, Shimizu S, Koyama Y, Yamada K, Kuwahara R, Kumamoto N, et al. DISC1 regulates cell–cell adhesion, cell–matrix adhesion and neurite outgrowth. Mol Psychiatry 2010; 15: 798–809.

    Article  CAS  Google Scholar 

  48. Walsh MT, Ryan M, Hillmann A, Condren R, Kenny D, Dinan T, et al. Elevated expression of integrin alpha(IIb) beta(IIIa) in drug-naive, first-episode schizophrenic patients. Biol Psychiatry 2002; 52: 874–879.

    Article  CAS  PubMed  Google Scholar 

  49. Singh KK, De RG, Drane L, Mao Y, Flood Z, Madison J, et al. Common DISC1 polymorphisms disrupt Wnt/GSK3beta signaling and brain development. Neuron 2011; 72: 545–558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature 2011; 473: 221–225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Freyberg Z, Ferrando SJ, Javitch JA . Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action. Am J Psychiatry. 2010; 167: 388–396.

    Article  PubMed  Google Scholar 

  52. Woo S, Rowan DJ, Gomez TM . Retinotopic mapping requires focal adhesion kinase-mediated regulation of growth cone adhesion. J Neurosci 2009; 29: 13981–13991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bechara A, Nawabi H, Moret F, Yaron A, Weaver E, Bozon M, et al. FAK-MAPK-dependent adhesion disassembly downstream of L1 contributes to semaphorin3A-induced collapse. EMBO J 2008; 27: 1549–1562.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Li W, Lee J, Vikis HG, Lee SH, Liu G, Aurandt J, et al. Activation of FAK and Src are receptor–proximal events required for netrin signaling. Nat Neurosci 2004; 7: 1213–1221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cho JY, Chak K, Andreone BJ, Wooley JR, Kolodkin AL . The extracellular matrix proteoglycan perlecan facilitates transmembrane semaphorin-mediated repulsive guidance. Genes Dev 2012; 26: 2222–2235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Myers JP, Santiago-Medina M, Gomez TM . Regulation of axonal outgrowth and pathfinding by integrin–ECM interactions. Dev Neurobiol 2011; 71: 901–923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Straub RE, Jiang Y, MacLean CJ, Ma Y, Webb BT, Myakishev MV, et al. Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am J Hum Genet 2002; 71: 337–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ryder PV, Faundez V . Schizophrenia: the 'BLOC' may be in the endosomes. Sci Signal 2009; 2: e66.

    Article  Google Scholar 

  59. Faundez V, Horng JT, Kelly RB . A function for the AP3 coat complex in synaptic vesicle formation from endosomes. Cell 1998; 93: 423–432.

    Article  CAS  PubMed  Google Scholar 

  60. Newell-Litwa K, Salazar G, Smith Y, Faundez V . Roles of BLOC-1 and adaptor protein-3 complexes in cargo sorting to synaptic vesicles. Mol Biol Cell 2009; 20: 1441–1453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Di Pietro SM, Falcon-Perez JM, Tenza D, Setty SR, Marks MS, Raposo G, et al. BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes. Mol Biol Cell 2006; 17: 4027–4038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Larimore J, Tornieri K, Ryder PV, Gokhale A, Zlatic SA, Craige B, et al. The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse. Mol Biol Cell 2011; 22: 4854–4867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gokhale A, Larimore J, Werner E, So L, Moreno-De-Luca A, Lese-Martin C, et al. Quantitative proteomic and genetic analyses of the schizophrenia susceptibility factor dysbindin identify novel roles of the biogenesis of lysosome-related organelles complex 1. J Neurosci 2012; 32: 3697–3711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Schubert KO, Focking M, Prehn JH, Cotter DR . Hypothesis review: are clathrin-mediated endocytosis and clathrin-dependent membrane and protein trafficking core pathophysiological processes in schizophrenia and bipolar disorder? Mol Psychiatry 2012; 17: 669–681.

    Article  CAS  PubMed  Google Scholar 

  65. Focking M, Dicker P, English JA, Schubert KO, Dunn MJ, Cotter DR . Common proteomic changes in the hippocampus in schizophrenia and bipolar disorder and particular evidence for involvement of cornu ammonis regions 2 and 3. Arch Gen Psychiatry 2011; 68: 477–488.

    Article  CAS  PubMed  Google Scholar 

  66. Guo AY, Sun J, Riley BP, Thiselton DL, Kendler KS, Zhao Z . The dystrobrevin-binding protein 1 gene: features and networks. Mol Psychiatry 2009; 14: 18–29.

    Article  CAS  PubMed  Google Scholar 

  67. Hodgkinson CA, Goldman D, Jaeger J, Persaud S, Kane JM, Lipsky RH, et al. Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am J Hum Genet 2004; 75: 862–872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wang Q, Brandon NJ . Regulation of the cytoskeleton by disrupted-in- schizophrenia 1 (DISC1). Mol Cell Neurosci 2011; 48: 359–364.

    Article  CAS  PubMed  Google Scholar 

  69. Kirov G, Pocklington AJ, Holmans P, Ivanov D, Ikeda M, Ruderfer D, et al. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol Psychiatry 2012; 17: 142–153.

    Article  CAS  PubMed  Google Scholar 

  70. 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: 179–184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Myers JP, Robles E, Ducharme-Smith A, Gomez TM . Focal adhesion kinase modulates Cdc42 activity downstream of positive and negative axon guidance cues. J Cell Sci 2012; 125: 2918–2929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Chen X, Sun C, Chen Q, O'Neill FA, Walsh D, Fanous AH, et al. Apoptotic engulfment pathway and schizophrenia. PLoS One 2009; 4: e6875.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Jarskog LF, Glantz LA, Gilmore JH, Lieberman JA . Apoptotic mechanisms in the pathophysiology of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 846–858.

    Article  CAS  PubMed  Google Scholar 

  74. Miuller N, Schwarz MJ . The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view. J Neural Transm Suppl 2007; 269–280.

  75. Nunes SO, Matsuo T, Kaminami MS, Watanabe MA, Reiche EM, Itano EN . An autoimmune or an inflammatory process in patients with schizophrenia, schizoaffective disorder, and in their biological relatives. Schizophr Res 2006; 84: 180–182.

    Article  PubMed  Google Scholar 

  76. Xu J, Sun J, Chen J, Wang L, Li A, Helm M, et al. RNA-Seq analysis implicates dysregulation of the immune system in schizophrenia. BMC Genom 2012; 13 (Suppl 8): S2.

    Article  Google Scholar 

  77. Erk S, Meyer-Lindenberg A, Schmierer P, Mohnke S, Grimm O, Garbusow M, et al. Hippocampal and frontolimbic function as intermediate phenotype for psychosis: evidence from healthy relatives and a common risk variant in CACNA1C. Biol Psychiatry 2013; S0006-3223: 01067–6.

    Google Scholar 

Download references

Acknowledgements

This study was supported by an Independent Investigator Award from NARSAD to XC, and by National Institutes of Health Grant (R01LM011177). We thank the Stanley Medical Institute for providing the brain specimens for transcriptome sequencing. We are grateful to the PGC investigators for providing their data to the NIMH Genetics Repository. We also thank three reviewers for their valuable comments, which improved the quality of this manuscript.

Author information

Author notes

  1. Z Zhao, J Xu and J Chen: The first three authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Biomedical Informatics and Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA

    Z Zhao, H Yu, J Sun, Q Wang & P Jia

  2. Beijing Genomics Institute (BGI), Shenzhen, Guangdong, China

    J Xu, F Xu, Y Zhang & Z Peng

  3. Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

    J Chen, M Reimers, S-A Bacanu, K S Kendler & X Chen

  4. Stanley Laboratory of Brain Research, Rockville, MD, USA

    S Kim

  5. Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA

    C Liu

Authors
  1. Z Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Reimers
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S-A Bacanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Q Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. P Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. F Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Y Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. K S Kendler
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Z Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. X Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to X Chen.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Molecular Psychiatry website

Supplementary information

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, Z., Xu, J., Chen, J. et al. Transcriptome sequencing and genome-wide association analyses reveal lysosomal function and actin cytoskeleton remodeling in schizophrenia and bipolar disorder. Mol Psychiatry 20, 563–572 (2015). https://doi.org/10.1038/mp.2014.82

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2014.82

This article is cited by

Search

Advanced search

Quick links