Currently recognized genes for schizophrenia: High-resolution chromosome ideogram representation.

Merlin G Butler, Austen B McGuire, Humaira Masoud, Ann M Manzardo
Author Information
  1. Merlin G Butler: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas.
  2. Austen B McGuire: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas.
  3. Humaira Masoud: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas.
  4. Ann M Manzardo: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas.

Abstract

A large body of genetic data from schizophrenia-related research has identified an assortment of genes and disturbed pathways supporting involvement of complex genetic components for schizophrenia spectrum and other psychotic disorders. Advances in genetic technology and expanding studies with searchable genomic databases have led to multiple published reports, allowing us to compile a master list of known, clinically relevant, or susceptibility genes contributing to schizophrenia. We searched key words related to schizophrenia and genetics from peer-reviewed medical literature sources, authoritative public access psychiatric websites and genomic databases dedicated to gene discovery and characterization of schizophrenia. Our list of 560 genes were arranged in alphabetical order in tabular form with gene symbols placed on high-resolution human chromosome ideograms. Genome wide pathway analysis using GeneAnalytics was carried out on the resulting list of genes to assess the underlying genetic architecture for schizophrenia. Recognized genes of clinical relevance, susceptibility or causation impact a broad range of biological pathways and mechanisms including ion channels (e.g., CACNA1B, CACNA1C, CACNA1H), metabolism (e.g., CYP1A2, CYP2C19, CYP2D6), multiple targets of neurotransmitter pathways impacting dopamine, GABA, glutamate, and serotonin function, brain development (e.g., NRG1, RELN), signaling peptides (e.g., PIK3CA, PIK4CA) and immune function (e.g., HLA-DRB1, HLA-DQA1) and interleukins (e.g., IL1A, IL10, IL6). This summary will enable clinical and laboratory geneticists, genetic counselors, and other clinicians to access convenient pictorial images of the distribution and location of contributing genes to inform diagnosis and gene-based treatment as well as provide risk estimates for genetic counseling of families with affected relatives.

Keywords

References

  1. Am J Med Genet. 2000 Spring;97(1):12-7 [PMID: 10813800]
  2. Brain Res Mol Brain Res. 2000 Oct 20;82(1-2):95-100 [PMID: 11042361]
  3. Arch Gen Psychiatry. 2000 Nov;57(11):1061-9 [PMID: 11074872]
  4. Neuron. 2000 Oct;28(1):53-67 [PMID: 11086983]
  5. Genomics. 2002 Feb;79(2):197-209 [PMID: 11829490]
  6. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4680-5 [PMID: 11930015]
  7. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13675-80 [PMID: 12364586]
  8. Bipolar Disord. 2002;4 Suppl 1:70-2 [PMID: 12479683]
  9. Biol Psychiatry. 2003 Apr 1;53(7):617-9 [PMID: 12679240]
  10. Hum Hered. 2002;54(4):199-209 [PMID: 12771552]
  11. Genomics. 2003 Aug;82(2):162-71 [PMID: 12837267]
  12. Hum Mol Genet. 2004 Mar 1;13(5):551-61 [PMID: 14709596]
  13. Mol Psychiatry. 2005 Jan;10(1):40-68; image 5 [PMID: 15263907]
  14. Am J Hum Genet. 2004 Oct;75(4):624-38 [PMID: 15329799]
  15. Mol Psychiatry. 2005 May;10(5):470-8 [PMID: 15452587]
  16. Ann Med. 2004;36(5):367-78 [PMID: 15478311]
  17. Hum Mutat. 2004 Dec;24(6):534-5 [PMID: 15532024]
  18. PLoS Med. 2005 Jul;2(7):e212 [PMID: 16033310]
  19. Mol Psychiatry. 2005 Dec;10(12):1074-88, 1057 [PMID: 16172613]
  20. Arch Gen Psychiatry. 2005 Nov;62(11):1205-13 [PMID: 16275808]
  21. Science. 2005 Nov 18;310(5751):1187-91 [PMID: 16293762]
  22. Proc Natl Acad Sci U S A. 2006 May 9;103(19):7482-7 [PMID: 16641098]
  23. Psychiatr Genet. 2006 Jun;16(3):105-15 [PMID: 16691128]
  24. Eur J Hum Genet. 2006 Jun;14(6):669-80 [PMID: 16721403]
  25. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12469-74 [PMID: 16891421]
  26. Am J Hum Genet. 2006 Sep;79(3):586-92 [PMID: 16909399]
  27. Brain Res. 2006 Nov 22;1121(1):1-11 [PMID: 17010949]
  28. Brain Behav Immun. 2007 May;21(4):450-7 [PMID: 17234379]
  29. J Clin Invest. 2007 Mar;117(3):672-82 [PMID: 17290303]
  30. Am J Hum Genet. 2007 Apr;80(4):664-72 [PMID: 17357072]
  31. Schizophr Res. 2007 Nov;96(1-3):100-11 [PMID: 17766091]
  32. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16621-6 [PMID: 17921251]
  33. Hum Mol Genet. 2008 Feb 1;17(3):458-65 [PMID: 17989066]
  34. Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1173-81 [PMID: 18361404]
  35. Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):6133-8 [PMID: 18413613]
  36. Nat Genet. 2008 Jul;40(7):827-34 [PMID: 18583979]
  37. Hum Mol Genet. 2008 Oct 15;17(20):3212-22 [PMID: 18658164]
  38. Schizophr Res. 2008 Sep;104(1-3):96-107 [PMID: 18715757]
  39. Mol Psychiatry. 2009 Apr;14(4):416-28 [PMID: 19065146]
  40. Lancet. 2009 Jan 17;373(9659):234-9 [PMID: 19150704]
  41. J Psychiatr Res. 2009 Oct;43(15):1195-9 [PMID: 19435634]
  42. Nature. 2009 Aug 6;460(7256):744-7 [PMID: 19571808]
  43. Nature. 2009 Aug 6;460(7256):753-7 [PMID: 19571809]
  44. Nature. 2009 Aug 6;460(7256):748-52 [PMID: 19571811]
  45. Am J Med Genet B Neuropsychiatr Genet. 2010 Apr 5;153B(3):786-91 [PMID: 19908236]
  46. Am J Hum Genet. 2009 Dec;85(6):833-46 [PMID: 19944402]
  47. Schizophr Res. 2010 Feb;116(2-3):126-32 [PMID: 20051317]
  48. Hum Mol Genet. 2010 Apr 1;19(7):1379-86 [PMID: 20071346]
  49. J Psychiatr Res. 2010 Sep;44(12):748-53 [PMID: 20185149]
  50. Schizophr Res. 2010 Jul;120(1-3):131-42 [PMID: 20347268]
  51. Mol Biol Rep. 2011 Jan;38(1):349-54 [PMID: 20364331]
  52. Mol Psychiatry. 2011 Apr;16(4):429-41 [PMID: 20368704]
  53. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7863-8 [PMID: 20385823]
  54. Hum Mol Genet. 2010 Jul 15;19(14):2841-57 [PMID: 20457675]
  55. Schizophr Res. 2010 Jul;120(1-3):143-9 [PMID: 20466522]
  56. Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1240-3 [PMID: 20468070]
  57. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15619-24 [PMID: 20713722]
  58. PLoS One. 2010 Aug 18;5(8):e12233 [PMID: 20805880]
  59. Biol Psychiatry. 2011 Mar 1;69(5):472-8 [PMID: 20832056]
  60. Mol Psychiatry. 2011 Nov;16(11):1117-29 [PMID: 20838396]
  61. Schizophr Res. 2010 Dec;124(1-3):192-9 [PMID: 20889312]
  62. Pediatr Res. 2011 May;69(5 Pt 2):26R-33R [PMID: 21289540]
  63. Nature. 2011 Mar 24;471(7339):499-503 [PMID: 21346763]
  64. Psychiatr Genet. 2011 Dec;21(6):315-8 [PMID: 21399567]
  65. Nat Med. 2011 Apr;17(4):470-8 [PMID: 21441918]
  66. Lancet Oncol. 2011 Jun;12(6):604-8 [PMID: 21498115]
  67. Int J Neuropsychopharmacol. 2012 May;15(4):459-69 [PMID: 21682944]
  68. Schizophr Res. 2011 Sep;131(1-3):43-51 [PMID: 21752600]
  69. Nat Genet. 2011 Sep 18;43(10):969-76 [PMID: 21926974]
  70. World J Biol Psychiatry. 2013 Mar;14(2):114-20 [PMID: 21936766]
  71. Nat Genet. 2011 Oct 30;43(12):1224-7 [PMID: 22037555]
  72. PLoS One. 2011;6(12):e28929 [PMID: 22205981]
  73. Behav Brain Funct. 2012 Jan 06;8:2 [PMID: 22225629]
  74. PLoS One. 2012;7(1):e30237 [PMID: 22276163]
  75. Eur J Hum Genet. 2012 Sep;20(9):1004-8 [PMID: 22433715]
  76. Neurosci Lett. 2012 Jul 19;521(2):93-7 [PMID: 22640896]
  77. PLoS Comput Biol. 2012;8(7):e1002587 [PMID: 22792057]
  78. Psychiatr Genet. 2013 Feb;23(1):20-8 [PMID: 23196875]
  79. Biol Psychiatry. 2013 Mar 15;73(6):532-9 [PMID: 23237318]
  80. PLoS One. 2013;8(1):e51674 [PMID: 23382809]
  81. Hum Mol Genet. 2013 May 15;22(10):2055-66 [PMID: 23393157]
  82. Front Genet. 2013 Apr 26;4:58 [PMID: 23637704]
  83. JAMA Psychiatry. 2013 Jun;70(6):573-81 [PMID: 23894747]
  84. Hum Mol Genet. 2013 Dec 15;22(24):5001-14 [PMID: 23904455]
  85. PLoS One. 2013 Aug 13;8(8):e70964 [PMID: 23967141]
  86. Nat Genet. 2013 Oct;45(10):1150-9 [PMID: 23974872]
  87. Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 2):2788-93 [PMID: 24091023]
  88. Neuropsychopharmacology. 2014 Mar;39(4):934-43 [PMID: 24141571]
  89. Eur Neuropsychopharmacol. 2014 Jan;24(1):65-85 [PMID: 24220657]
  90. Pharmacogenomics. 2013 Dec;14(16):2067-83 [PMID: 24279860]
  91. Neuron. 2014 Jan 22;81(2):306-13 [PMID: 24389010]
  92. Transl Psychiatry. 2014 Jan 07;4:e339 [PMID: 24399042]
  93. Front Cell Neurosci. 2014 Jan 21;8:5 [PMID: 24478629]
  94. Science. 2014 Jun 6;344(6188):1178-82 [PMID: 24904170]
  95. Biomed Rep. 2014 Sep;2(5):729-736 [PMID: 25054019]
  96. Nature. 2014 Jul 24;511(7510):421-7 [PMID: 25056061]
  97. Schizophr Bull. 2015 May;41(3):715-27 [PMID: 25380769]
  98. Mol Psychiatry. 2015 Feb;20(1):72-6 [PMID: 25385368]
  99. Curr Opin Neurobiol. 2015 Feb;30:131-8 [PMID: 25544106]
  100. Schizophr Bull. 2015 Mar;41(2):313-4 [PMID: 25634913]
  101. Int J Mol Sci. 2015 Feb 20;16(3):4416-28 [PMID: 25710722]
  102. Int J Mol Sci. 2015 Mar 20;16(3):6464-95 [PMID: 25803107]
  103. Neuropsychobiology. 2015;71(3):158-67 [PMID: 25998553]
  104. Value Health. 2014 Nov;17(7):A767 [PMID: 27202817]
  105. Am J Hum Genet. 1984 Jan;36(1):36-43 [PMID: 6695924]
  106. Schizophr Bull. 1993;19(2):261-85 [PMID: 8322035]
  107. Am J Hum Genet. 1996 Sep;59(3):731-6 [PMID: 8751875]
  108. Lancet. 1997 Apr 26;349(9060):1221 [PMID: 9130948]
  109. Am J Psychiatry. 1998 Jan;155(1):76-83 [PMID: 9433342]
  110. Mol Psychiatry. 1998 Jan;3(1):32-7 [PMID: 9491810]
  111. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4667-72 [PMID: 9539796]
  112. Mol Psychiatry. 1998 Mar;3(2):141-9 [PMID: 9577838]

Grants

  1. P30 HD002528/NICHD NIH HHS
  2. HD02528/NICHD NIH HHS

MeSH Term

Chromosome Banding
Chromosomes, Human
Genetic Predisposition to Disease
Humans
Reelin Protein
Schizophrenia

Word Cloud

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