title: Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms.
abstract: OBJECTIVE
  Alcoholism arises from combined effects of multiple biological factors including genetic and non-genetic causes with gene/environmental interaction. Intensive research and advanced genetic technology has generated a long list of genes and biomarkers involved in alcoholism neuropathology. These markers reflect complex overlapping and competing effects of possibly hundreds of genes which impact brain structure, function, biochemical alcohol processing, sensitivity and risk for dependence.
  
  
  METHODS
  We compiled a tabular list of clinically relevant genetic biomarkers for alcoholism targeting expression disturbances in the human brain through an extensive search of keywords related to alcoholism, alcohol abuse, and genetics from peer reviewed medical research articles and related nationally sponsored websites. Gene symbols were then placed on high resolution human chromosome ideograms with gene descriptions in tabular form.
  
  
  RESULTS
  We identified 337 clinically relevant genetic biomarkers and candidate genes for alcoholism and alcohol-responsiveness from human brain research. Genetic biomarkers included neurotransmitter pathways associated with brain reward processes for dopaminergic (e.g., DRD2, MAOA, and COMT), serotoninergic (e.g., HTR3A, HTR1B, HTR3B, and SLC6A4), GABAergic (e.g., GABRA1, GABRA2, and GABRG1), glutaminergic (GAD1, GRIK3, and GRIN2C) and opioid (e.g., OPRM1, OPRD1, and OPRK1) pathways which presumably impact reinforcing properties of alcohol. Gene level disturbances in cellular and molecular networks impacted by alcohol and alcoholism pathology include transketolase (TKT), transferrin (TF), and myelin (e.g., MBP, MOBP, and MOG).
  
  
  CONCLUSIONS
  High resolution chromosome ideograms provide investigators, physicians, geneticists and counselors a convenient visual image of the distribution of alcoholism genetic biomarkers from brain research with alphabetical listing of genes in tabular form allowing comparison between alcoholism-related phenotypes, and clinically-relevant alcoholism gene(s) at the chromosome band level to guide research, diagnosis, and treatment. Chromosome ideograms may facilitate gene-based personalized counseling of alcohol dependent individuals and their families.
authors: Department of Psychiatry & Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: amanzardo@kumc.edu.
authors: Ann M
authors: AM
authors: Manzardo
authors: Department of Psychiatry & Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Austen
authors: A
authors: McGuire
authors: Department of Psychiatry & Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Merlin G
authors: MG
authors: Butler
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002877:Chromosomes, Human / Q000235:genetics*; D015870:Gene Expression; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans
chemical_list: D015415:Biomarkers; D005819:Genetic Markers
keywords: Alcoholism; Brain; Chromosome band location; Gene; Genetic biomarkers; High resolution chromosome ideograms
references: Am J Med Genet. 2000 Jul 17;93(2):117-21
references: 10869113
references: Alcohol Clin Exp Res. 2000 Dec;24(12):1873-82
references: 11141048
references: J Neurochem. 2002 May;81(4):802-13
references: 12065639
references: J Neurosci Res. 2003 Jun 15;72(6):756-67
references: 12774316
references: Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128B(1):102-13
references: 15211641
references: Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):110-5
references: 15274051
references: J Neurochem. 2004 Sep;90(5):1050-8
references: 15312160
references: Alcohol Clin Exp Res. 2004 Dec;28(12):1789-95
references: 15608594
references: Arch Gen Psychiatry. 2005 Jan;62(1):47-55
references: 15630072
references: Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):79-84
references: 15635638
references: Hum Mol Genet. 2005 Apr 1;14(7):967-71
references: 15731118
references: J Neurochem. 2005 Apr;93(2):359-70
references: 15816859
references: Am J Psychiatry. 2005 May;162(5):1003-5
references: 15863807
references: Hum Mol Genet. 2005 Aug 15;14(16):2421-34
references: 16000316
references: Am J Psychiatry. 2005 Aug;162(8):1483-93
references: 16055769
references: Neuropsychopharmacology. 2006 Jul;31(7):1574-82
references: 16292326
references: Am J Hum Genet. 2006 Jan;78(1):103-11
references: 16385453
references: Genes Brain Behav. 2006;5 Suppl 1:78-84
references: 16417620
references: Hum Mol Genet. 2006 May 1;15(9):1539-49
references: 16571603
references: Behav Genet. 2006 Sep;36(5):640-50
references: 16622805
references: Addict Biol. 2006 Sep;11(3-4):386-96
references: 16961766
references: Alcohol Clin Exp Res. 2006 Nov;30(11):1807-16
references: 17067344
references: Am J Med Genet B Neuropsychiatr Genet. 2007 Jul 5;144B(5):596-604
references: 17226798
references: Alcohol Clin Exp Res. 2007 Feb;31(2):209-15
references: 17250611
references: Addict Biol. 2007 Sep;12(3-4):496-502
references: 17559549
references: Mol Psychiatry. 2008 May;13(5):531-43
references: 17622222
references: Alcohol Clin Exp Res. 2007 Sep;31(9):1460-6
references: 17625000
references: Alcohol Res Health. 2007;30(1):5-13
references: 17718394
references: Hum Mol Genet. 2007 Dec 1;16(23):2880-91
references: 17804423
references: Pharmacogenomics J. 2008 Jun;8(3):220-7
references: 17923853
references: Biol Psychiatry. 2008 Jun 1;63(11):1047-53
references: 18163977
references: Nat Genet. 2008 Feb;40(2):124-5
references: 18227866
references: Hum Mol Genet. 2008 Jun 15;17(12):1783-9
references: 18319328
references: Br J Pharmacol. 2008 May;154(2):275-87
references: 18362899
references: Mol Psychiatry. 2009 May;14(5):501-10
references: 18414406
references: Alcohol Clin Exp Res. 2008 Jun;32(6):1023-30
references: 18422838
references: Pharmacol Biochem Behav. 2008 Jul;90(1):95-104
references: 18440057
references: Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 5;150B(3):359-68
references: 18618593
references: Alcohol Clin Exp Res. 2008 Dec;32(12):2117-27
references: 18828801
references: Alcohol Clin Exp Res. 2008 Dec;32(12):2031-40
references: 18828811
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D840-5
references: 18978021
references: Hum Mol Genet. 2009 Feb 1;18(3):580-93
references: 18996923
references: Alcohol Clin Exp Res. 2009 Mar;33(3):428-34
references: 19120058
references: Hum Genet. 2009 Jun;125(5-6):605-13
references: 19306106
references: JAMA. 1990 Apr 18;263(15):2055-60
references: 1969501
references: Gastroenterology. 2009 Nov;137(5):1768-75
references: 19698717
references: JAMA. 1990 Dec 26;264(24):3156-60
references: 1979357
references: Alcohol Clin Exp Res. 2010 May;34(5):840-52
references: 20201924
references: Alcohol Clin Exp Res. 2010 May;34(5):800-12
references: 20201926
references: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5082-7
references: 20202923
references: Clin Exp Allergy. 2010 Jan;40(1):123-30
references: 20205700
references: Hum Mol Genet. 2010 Jun 15;19(12):2497-506
references: 20332099
references: Alcohol Clin Exp Res. 2010 Jul;34(7):1291-302
references: 20477762
references: Am J Med Genet B Neuropsychiatr Genet. 2011 Jan;156B(1):44-58
references: 21184583
references: Alcohol Clin Exp Res. 2011 Apr;35(4):595-605
references: 21223300
references: J Neural Transm (Vienna). 2011 Sep;118(9):1293-9
references: 21445666
references: Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7119-24
references: 21471458
references: Biol Psychiatry. 2011 Sep 15;70(6):513-8
references: 21529783
references: J Psychiatr Res. 2011 Nov;45(11):1419-25
references: 21703634
references: Curr Top Behav Neurosci. 2013;13:3-30
references: 21744309
references: Neuropsychopharmacology. 2012 Jan;37(2):557-66
references: 21956439
references: J Neural Transm (Vienna). 2012 Apr;119(4):425-33
references: 22072270
references: PLoS One. 2011;6(11):e26726
references: 22096494
references: PLoS One. 2011;6(12):e28477
references: 22205951
references: Genome Biol. 2012 Feb 20;13(2):239
references: 22348705
references: Genes Brain Behav. 2012 Aug;11(6):712-9
references: 22554406
references: Alcohol Clin Exp Res. 2012 Dec;36(12):2074-85
references: 22577853
references: Chin Med J (Engl). 2012 Mar;125(6):1127-34
references: 22613542
references: Pharmacol Biochem Behav. 2012 Dec;103(2):253-9
references: 22954510
references: Alcohol Res. 2012;34(3):336-8
references: 23134049
references: Ann N Y Acad Sci. 2013 Apr;1282:39-70
references: 23170934
references: Alcohol Clin Exp Res. 2013 May;37(5):730-9
references: 23216389
references: BMC Genomics. 2012;13 Suppl 8:S16
references: 23282140
references: Am J Med Genet B Neuropsychiatr Genet. 2013 Mar;162B(2):169-76
references: 23335468
references: Addict Biol. 2014 Jul;19(4):708-21
references: 23362995
references: Curr Opin Neurobiol. 2013 Aug;23(4):513-20
references: 23434064
references: Drug Alcohol Depend. 2013 May 1;129(3):254-64
references: 23455491
references: Alcohol Res. 2012;34(4):391-400
references: 23584105
references: Alcohol Res. 2012;34(4):408-13
references: 23584107
references: Nat Rev Gastroenterol Hepatol. 2013 Aug;10(8):487-94
references: 23712313
references: Hum Genet. 2013 Oct;132(10):1141-51
references: 23743675
references: J Neural Transm (Vienna). 2014 Jan;121(1):105-11
references: 23846846
references: J Psychiatr Res. 2013 Nov;47(11):1717-24
references: 23953852
references: Alcohol Clin Exp Res. 2014 Feb;38(2):354-66
references: 24015780
references: Curr Psychiatry Rep. 2013 Nov;15(11):412
references: 24091936
references: Mol Genet Genomics. 2014 Jun;289(3):253-69
references: 24395673
references: Alcohol Clin Exp Res. 2014 Jun;38(6):1594-601
references: 24890784
references: Drug Alcohol Depend. 2014 Sep 1;142:56-62
references: 24962325
references: Am J Med Genet. 1998 May 8;81(3):207-15
references: 9603606
references: Am J Med Genet. 1998 May 8;81(3):216-21
references: 9603607
references: Arch Gen Psychiatry. 1998 Nov;55(11):982-8
references: 9819066