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J Neurotrauma. 2017 Jul 15;34(14):2280-2290. doi: 10.1089/neu.2016.4856. Epub 2017 May 03.

Applying Systems Biology Methodology To Identify Genetic Factors Possibly Associated with Recovery after Traumatic Brain Injury.

Journal of neurotrauma

Brad G Kurowski, Amery Treble-Barna, Alexis J Pitzer, Shari L Wade, Lisa J Martin, Ranjit S Chima, Anil Jegga

Affiliations

  1. 1 Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine , Cincinnati, Ohio.
  2. 2 Division of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
  3. 3 Department of Psychology, Xavier University , Cincinnati, Ohio.

PMID: 28301983 PMCID: PMC5510694 DOI: 10.1089/neu.2016.4856

Abstract

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality worldwide. It is linked with a number of medical, neurological, cognitive, and behavioral sequelae. The influence of genetic factors on the biology and related recovery after TBI is poorly understood. Studies that seek to elucidate the impact of genetic influences on neurorecovery after TBI will lead to better individualization of prognosis and inform development of novel treatments, which are considerably lacking. Current genetic studies related to TBI have focused on specific candidate genes. The objectives of this study were to use a system biology-based approach to identify biologic processes over-represented with genetic variants previously implicated in clinical outcomes after TBI and identify unique genes potentially related to recovery after TBI. After performing a systematic review to identify genes in the literature associated with clinical outcomes, we used the genes identified to perform a systems biology-based integrative computational analysis to ascertain the interactions between molecular components and to develop models for regulation and function of genes involved in TBI recovery. The analysis identified over-representation of genetic variants primarily in two biologic processes: response to injury (cell proliferation, cell death, inflammatory response, and cellular metabolism) and neurocognitive and behavioral reserve (brain development, cognition, and behavior). Overall, this study demonstrates the use of a systems biology-based approach to identify unique/novel genes or sets of genes important to the recovery process. Findings from this systems biology-based approach provide additional insight into the potential impact of genetic variants on the underlying complex biological processes important to TBI recovery and may inform the development of empirical genetic-related studies for TBI. Future studies that combine systems biology methodology and genomic, proteomic, and epigenetic approaches are needed in TBI.

Keywords: genetic factors; recovery; rehabilitation; traumatic brain injury

References

  1. Arch Phys Med Rehabil. 1996 Mar;77(3):223-31 - PubMed
  2. J Neurotrauma. 2014 Dec 1;31(23):1920-6 - PubMed
  3. Methods Mol Biol. 2011;700:241-59 - PubMed
  4. Curr Pharm Des. 2014;20(26):4275-83 - PubMed
  5. Clin Neuropathol. 2006 Nov-Dec;25(6):255-64 - PubMed
  6. Brain Inj. 2011;25(4):365-9 - PubMed
  7. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 - PubMed
  8. Addict Biol. 2013 Mar;18(2):344-56 - PubMed
  9. Acta Neurochir (Wien). 2012 Apr;154(4):675-80; discussion 680 - PubMed
  10. Neurosurgery. 2009 Apr;64(4):698-704; discussion 704 - PubMed
  11. J Head Trauma Rehabil. 2015 Nov-Dec;30(6):E54-66 - PubMed
  12. Ann Neurol. 2014 Feb;75(2):186-95 - PubMed
  13. Brain. 2005 Nov;128(Pt 11):2556-61 - PubMed
  14. J Neurotrauma. 2011 Sep;28(9):1683-92 - PubMed
  15. Brain. 2008 Feb;131(Pt 2):543-58 - PubMed
  16. Neurogenetics. 2015 Jul;16(3):169-80 - PubMed
  17. Dev Psychopathol. 2013 May;25(2):291-306 - PubMed
  18. Funct Neurol. 2006 Oct-Dec;21(4):223-8 - PubMed
  19. Curr Pharm Des. 2001 Oct;7(15):1475-503 - PubMed
  20. Dev Neuropsychol. 2004;25(1-2):199-225 - PubMed
  21. Neurochem Res. 2007 Apr-May;32(4-5):905-15 - PubMed
  22. Arch Neurol. 2003 Jun;60(6):818-22 - PubMed
  23. J Neurotrauma. 2013 Aug 15;30(16):1415-25 - PubMed
  24. PM R. 2010 Dec;2(12 Suppl 2):S241-52 - PubMed
  25. Epilepsia. 2014 Jul;55(7):1109-19 - PubMed
  26. Genome Res. 2011 May;21(5):658-64 - PubMed
  27. Am J Psychiatry. 2005 Sep;162(9):1749-51 - PubMed
  28. J Neurotrauma. 2010 Aug;27(8):1413-27 - PubMed
  29. J Neurotrauma. 2006 Nov;23(11):1600-8 - PubMed
  30. Acta Neurochir (Wien). 2005 Jul;147(7):715-20; discussion 720 - PubMed
  31. Brain Inj. 2012;26(13-14):1658-69 - PubMed
  32. Parkinsonism Relat Disord. 2015 Mar;21(3):292-6 - PubMed
  33. Front Neurol. 2013 May 31;4:61 - PubMed
  34. Crit Care Med. 2014 Oct;42(10):2258-66 - PubMed
  35. Circ Cardiovasc Genet. 2013 Jun;6(3):279-89 - PubMed
  36. Childs Nerv Syst. 2008 Mar;24(3):349-56 - PubMed
  37. Ann N Y Acad Sci. 1996 Dec 16;802:6-15 - PubMed
  38. J Neurotrauma. 2012 Apr 10;29(6):1111-8 - PubMed
  39. Pharmgenomics Pers Med. 2015 Jan 16;8:9-22 - PubMed
  40. Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11 - PubMed
  41. Neurology. 2004 Jun 8;62(11):1963-6 - PubMed
  42. J Neurol Neurosurg Psychiatry. 2006 Oct;77(10):1191-3 - PubMed
  43. Am J Hum Genet. 2011 Jun 10;88(6):755-766 - PubMed
  44. J Neuropsychiatry Clin Neurosci. 2006 Winter;18(1):39-44 - PubMed
  45. Pediatr Crit Care Med. 2000 Jul;1(1):4-19 - PubMed
  46. Eur J Neurol. 2001 Nov;8(6):707-10 - PubMed
  47. Intensive Care Med. 2005 Sep;31(9):1168-73 - PubMed
  48. Autophagy. 2011 May;7(5):477-89 - PubMed
  49. Pharmgenomics Pers Med. 2014 Aug 13;7:227-40 - PubMed
  50. J Abnorm Child Psychol. 2011 Jan;39(1):1-10 - PubMed
  51. PM R. 2011 Jun;3(6 Suppl 1):S52-8 - PubMed
  52. J Int Neuropsychol Soc. 2008 Sep;14(5):734-45 - PubMed
  53. Epilepsy Behav. 2009 Nov;16(3):501-6 - PubMed
  54. PLoS One. 2011;6(7):e21636 - PubMed
  55. Neuroscientist. 2015 Aug;21(4):424-41 - PubMed
  56. Neurology. 1995 Mar;45(3 Pt 1):555-7 - PubMed
  57. Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1427-34 - PubMed
  58. J Neurotrauma. 2015 Dec 1;32(23):1849-60 - PubMed
  59. PLoS One. 2013 Apr 17;8(4):e61197 - PubMed
  60. J Clin Invest. 2014 May;124(5):2277-86 - PubMed
  61. J Neurol Sci. 2015 Feb 15;349(1-2):99-104 - PubMed
  62. Neurology. 2002 Apr 9;58(7):1038-44 - PubMed
  63. Neurorehabil Neural Repair. 2015 Mar-Apr;29(3):234-46 - PubMed
  64. J Neuropsychiatry Clin Neurosci. 2005 Fall;17(4):465-71 - PubMed
  65. Psychiatry J. 2014;2014:730956 - PubMed
  66. Eur J Neurol. 2015 May;22(5):874-8 - PubMed
  67. Neurosci Lett. 2006 Nov 13;408(2):155-8 - PubMed
  68. Brain Inj. 2015;29(7-8):963-70 - PubMed
  69. Transl Psychiatry. 2012 Jan 31;2:e75 - PubMed
  70. BMC Bioinformatics. 2009 Feb 27;10:73 - PubMed
  71. J Child Psychol Psychiatry. 2011 Oct;52(10):1044-51 - PubMed
  72. J Mol Neurosci. 2015 Jul;56(3):597-601 - PubMed
  73. Int Psychogeriatr. 2007 Feb;19(1):159-65 - PubMed
  74. Neurology. 2000 Mar 28;54(6):1316-23 - PubMed
  75. J Hum Hypertens. 2015 May;29(5):283-91 - PubMed
  76. Pharmacogenet Genomics. 2015 Oct;25(10):485-90 - PubMed
  77. Psychiatr Genet. 2010 Dec;20(6):304-10 - PubMed
  78. J Neurotrauma. 2011 May;28(5):727-37 - PubMed
  79. Neuroscientist. 2012 Dec;18(6):631-44 - PubMed
  80. Fam Cancer. 2013 Dec;12(4):657-67 - PubMed
  81. Front Genet. 2014 Oct 14;5:314 - PubMed
  82. J Neurosci Res. 2015 Feb;93(2):199-214 - PubMed
  83. Neurosurg Focus. 2010 Jan;28(1):E9 - PubMed
  84. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):426-30 - PubMed
  85. J Neurotrauma. 2010 Mar;27(3):465-71 - PubMed
  86. J Neurosci. 2011 Jan 12;31(2):598-606 - PubMed
  87. J Neurotrauma. 2014 Jan 1;31(1):34-41 - PubMed
  88. Neurology. 1999 Dec 10;53(9):1959-62 - PubMed
  89. J Neurotrauma. 2010 Jun;27(6):999-1006 - PubMed
  90. Mol Neurobiol. 2013 Jun;47(3):957-66 - PubMed
  91. J Neurotrauma. 2007 May;24(5):790-7 - PubMed
  92. Neurology. 2003 Sep 9;61(5):683-5 - PubMed
  93. Biomed Eng Comput Biol. 2013 Jun 23;5:51-6 - PubMed
  94. J Neurosurg. 2003 Feb;98(2):302-6 - PubMed
  95. Brain Inj. 2013 Jun;27(6):696-706 - PubMed
  96. J Neurotrauma. 2013 Jul 1;30(13):1101-16 - PubMed
  97. Dev Psychopathol. 2013 May;25(2):555-75 - PubMed
  98. Neurocrit Care. 2013 Oct;19(2):192-8 - PubMed
  99. Emerg Med J. 2008 Nov;25(11):759-61 - PubMed
  100. BMC Bioinformatics. 2007 Oct 16;8:392 - PubMed
  101. Nat Neurosci. 2015 Dec;18(12):1832-44 - PubMed
  102. Lancet. 1997 Oct 11;350(9084):1069-71 - PubMed
  103. J Psychiatr Res. 2013 Jun;47(6):835-42 - PubMed
  104. J Neurotrauma. 2013 Oct 15;30(20):1710-6 - PubMed
  105. Acta Neurochir (Wien). 2003 Aug;145(8):649-53; discussion 653-4 - PubMed
  106. Eur J Neurol. 2005 Feb;12(2):86-92 - PubMed
  107. BMC Med Ethics. 2013 Dec 21;14:55 - PubMed
  108. J Pediatr Rehabil Med. 2012;5(3):217-31 - PubMed
  109. Acta Anaesthesiol Scand. 2008 Nov;52(10):1364-9 - PubMed
  110. Psychiatr Q. 2012 Mar;83(1):29-40 - PubMed
  111. J Int Neuropsychol Soc. 2014 Apr;20(4):444-54 - PubMed
  112. Dev Psychopathol. 2012 May;24(2):411-27 - PubMed
  113. Neurosci Lett. 2016 Jun 20;625:26-33 - PubMed
  114. J Neurotrauma. 2011 Sep;28(9):1739-45 - PubMed
  115. J Neurotrauma. 2012 Mar 1;29(4):621-8 - PubMed
  116. Br J Anaesth. 2007 Jul;99(1):4-9 - PubMed
  117. Neurology. 2000 Nov 28;55(10):1536-9 - PubMed
  118. Brain Inj. 2007 Sep;21(10):1049-54 - PubMed
  119. Neurology. 2002 Apr 9;58(7):1115-8 - PubMed
  120. J Head Trauma Rehabil. 2009 Jan-Feb;24(1):57-64 - PubMed
  121. Neurology. 1999 Jan 15;52(2):244-8 - PubMed
  122. Epilepsy Res. 2013 Feb;103(2-3):180-94 - PubMed
  123. Dev Neurosci. 2006;28(4-5):256-63 - PubMed
  124. Ann Neurol. 2012 Jan;71(1):40-8 - PubMed
  125. Am J Epidemiol. 1997 Sep 1;146(5):373-84 - PubMed
  126. Am J Med Genet A. 2013 Aug;161A(8):2030-5 - PubMed
  127. Surg Neurol. 2006 Jan;65(1):7-10; discussion 10 - PubMed
  128. Epilepsia. 2015 Aug;56(8):1198-206 - PubMed
  129. Neurology. 2004 Aug 24;63(4):749-50 - PubMed
  130. Neurosci Biobehav Rev. 2015 Aug;55:573-93 - PubMed
  131. Am J Med Genet B Neuropsychiatr Genet. 2011 Apr;156B(3):346-51 - PubMed
  132. Methods Mol Biol. 2014;1168:295-312 - PubMed
  133. Epilepsy Res. 2010 Aug;90(3):259-72 - PubMed
  134. PLoS One. 2011;6(11):e27389 - PubMed
  135. Brief Bioinform. 2010 Jan;11(1):96-110 - PubMed
  136. Dev Psychobiol. 2014 Apr;56(3):373-91 - PubMed
  137. Genet Mol Res. 2015 Sep 21;14(3):10948-53 - PubMed
  138. Brain Inj. 2013;27(11):1281-6 - PubMed
  139. Biomed Res Int. 2014;2014:293687 - PubMed
  140. Soc Cogn Affect Neurosci. 2013 Jun;8(5):499-508 - PubMed
  141. Brain Inj. 2010;24(6):886-92 - PubMed
  142. Pharmgenomics Pers Med. 2014 Nov 06;7:349-56 - PubMed
  143. Curr Opin Psychiatry. 2012 May;25(3):231-8 - PubMed
  144. Neurology. 2011 Mar 22;76(12):1038-45 - PubMed
  145. Childs Nerv Syst. 2009 Jan;25(1):47-54 - PubMed
  146. Neurology. 2005 Oct 11;65(7):1077-82 - PubMed
  147. Brain Inj. 2008 Aug;22(9):705-14 - PubMed
  148. J Lipid Res. 2006 Dec;47(12):2601-13 - PubMed
  149. J Neurotrauma. 2007 Dec;24(12):1802-10 - PubMed
  150. Dev Med Child Neurol. 2015 Jan;57(1):16-22 - PubMed
  151. J Neurol Neurosurg Psychiatry. 2003 Aug;74(8):1047-52 - PubMed
  152. Brain Imaging Behav. 2014 Sep;8(3):420-34 - PubMed

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