title: Association of a common genetic variant within ANKK1 with six-month cognitive performance after traumatic brain injury.
abstract: Genetic association analyses suggest that certain common single nucleotide polymorphisms (SNPs) may adversely impact recovery from traumatic brain injury (TBI). Delineating their causal relationship may aid in development of novel interventions and in identifying patients likely to respond to targeted therapies. We examined the influence of the (C/T) SNP rs1800497 of ANKK1 on post-TBI outcome using data from two prospective multicenter studies: the Citicoline Brain Injury Treatment (COBRIT) trial and Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot). We included patients with ANKK1 genotyping results and cognitive outcomes at six months post-TBI (n = 492: COBRIT n = 272, TRACK-TBI Pilot n = 220). Using the California Verbal Learning Test Second Edition (CVLT-II) Trial 1-5 Standard Score, we found a dose-dependent effect for the T allele, with T/T homozygotes scoring lowest on the CVLT-II Trial 1-5 Standard Score (T/T 45.1, C/T 51.1, C/C 52.1, ANOVA, p = 0.008). Post hoc testing with multiple comparison-correction indicated that T/T patients performed significantly worse than C/T and C/C patients. Similar effects were observed in a test of non-verbal processing (Wechsler Adult Intelligence Scale, Processing Speed Index). Our findings extend those of previous studies reporting a negative relationship of the ANKK1 T allele with cognitive performance after TBI. In this study, we demonstrate the value of pooling shared clinical, biomarker, and outcome variables from two large datasets applying the NIH TBI Common Data Elements. The results have implications for future multicenter investigations to further elucidate the role of ANKK1 in post-TBI outcome.
authors: Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
authors: John K
authors: JK
authors: Yue
authors: Angela M
authors: AM
authors: Pronger
authors: Adam R
authors: AR
authors: Ferguson
authors: Nancy R
authors: NR
authors: Temkin
authors: Sourabh
authors: S
authors: Sharma
authors: Jonathan
authors: J
authors: Rosand
authors: Marco D
authors: MD
authors: Sorani
authors: Thomas W
authors: TW
authors: McAllister
authors: Jason
authors: J
authors: Barber
authors: Ethan A
authors: EA
authors: Winkler
authors: Esteban G
authors: EG
authors: Burchard
authors: Donglei
authors: D
authors: Hu
authors: Hester F
authors: HF
authors: Lingsma
authors: Shelly R
authors: SR
authors: Cooper
authors: Ava M
authors: AM
authors: Puccio
authors: David O
authors: DO
authors: Okonkwo
authors: Ramon
authors: R
authors: Diaz-Arrastia
authors: Geoffrey T
authors: GT
authors: Manley
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000235:genetics* / Q000523:psychology* / Q000534:rehabilitation; D003071:Cognition; D005260:Female; D005838:Genotype; D006801:Humans; D007858:Learning; D008297:Male; D008568:Memory; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases
references: Arch Phys Med Rehabil. 2010 Nov;91(11):1661-6
references: 21044709
references: Mol Psychiatry. 1999 May;4(3):290-6
references: 10395223
references: J Pers Assess. 1985 Feb;49(1):71-5
references: 16367493
references: Mol Psychiatry. 2004 Dec;9(12 ):1060-1
references: 15278099
references: J Neurotrauma. 2013 Nov 15;30(22):1831-44
references: 23815563
references: Cell Mol Life Sci. 2012 Nov;69(22):3751-63
references: 22562581
references: Curr Diab Rep. 2010 Dec;10(6):452-66
references: 20878272
references: J Head Trauma Rehabil. 2006 Jul-Aug;21(4):361-74
references: 16915011
references: J Neurotrauma. 2014 Sep 1;31(17):1457-77
references: 24742275
references: Neurochem Res. 2007 Apr-May;32(4-5):905-15
references: 17342413
references: Arch Phys Med Rehabil. 2010 Nov;91(11):1637-40
references: 21044706
references: Neurosurgery. 2012 Jul;71(1):1-5
references: 22705717
references: Am J Psychiatry. 2005 Sep;162(9):1749-51
references: 16135640
references: J Neurotrauma. 2008 Jul;25(7):719-38
references: 18627252
references: J Hum Genet. 2010 Apr;55(4):195-206
references: 20300123
references: Brain Inj. 2004 Apr;18(4):331-50
references: 14742148
references: Arch Phys Med Rehabil. 2010 Nov;91(11):1692-6
references: 21044713
references: Neurotherapeutics. 2010 Jan;7(1):127-34
references: 20129504
references: Biochim Biophys Acta. 2014 Oct;1842(10):1903-1909
references: 24798234
references: JAMA. 2013 Aug 7;310(5):473-4
references: 23925611
references: Curr Neurol Neurosci Rep. 2013 Oct;13(10):381
references: 23954969
references: J Rehabil Med. 2004 Feb;(43 Suppl):28-60
references: 15083870
references: Curr Atheroscler Rep. 2005 May;7(3):235-41
references: 15811259
references: Arch Phys Med Rehabil. 2010 Nov;91(11):1650-1660.e17
references: 21044708
references: Sci Rep. 2013;3:1236
references: 23393618
references: Eur Psychiatry. 2003 Nov;18(7):356-60
references: 14643564
references: J Neurotrauma. 2012 Mar 20;29(5):735-46
references: 21970562
references: Nicotine Tob Res. 2007 Dec;9(12):1251-7
references: 18058343
references: J Neurotrauma. 2011 Feb;28(2):177-87
references: 21162610
references: J Neurosci. 2010 Jul 21;30(29):9788-92
references: 20660261
references: Trends Mol Med. 2005 May;11(5):217-24
references: 15882609
references: Neuroimage. 2010 Jan 1;49(1):1-8
references: 19744568
references: Biol Psychol. 2010 Sep;85(1):143-8
references: 20542080
references: Science. 2007 Dec 7;318(5856):1642-5
references: 18063800
references: J Neurotrauma. 1998 Aug;15(8):573-85
references: 9726257
references: Arch Phys Med Rehabil. 2010 Nov;91(11):1667-72
references: 21044710
references: Biol Psychiatry. 2010 Jan 1;67(1):3-11
references: 19853839
references: Neurosurg Focus. 2010 Jan;28(1):E9
references: 20043724
references: Neuroimage. 2006 Aug 1;32(1):16-22
references: 16626974
references: Brief Funct Genomics. 2011 Mar;10(2):52-60
references: 21436302
references: Neurosci Biobehav Rev. 2009 Jul;33(7):981-1003
references: 19580914
references: JAMA. 2012 Nov 21;308(19):1993-2000
references: 23168823
references: Mol Psychiatry. 2007 May;12(5):454-61
references: 17453061
references: Curr Drug Targets. 2007 Jul;8(7):850-9
references: 17630939
references: JAMA. 1991 Oct 2;266(13):1793-800
references: 1832466
references: Psychogeriatrics. 2012 Mar;12(1):62-73
references: 22416831
references: World J Diabetes. 2014 Apr 15;5(2):128-40
references: 24748926
references: Drug Discov Today. 2010 Sep;15(17-18):741-8
references: 20558318
references: Methods Mol Biol. 2008;448:379-93
references: 18370238
references: Exp Brain Res. 2010 Jul;204(1):57-70
references: 20496060
references: J Am Coll Cardiol. 2008 Jul 22;52(4):241-50
references: 18634977
references: Am J Med Genet B Neuropsychiatr Genet. 2003 Jan 1;116B(1):103-25
references: 12497624
references: Hum Mutat. 2004 Jun;23(6):540-5
references: 15146457
references: Lancet Neurol. 2013 Jan;12(1):92-104
references: 23237904
references: J Rehabil Med. 2004 Feb;(43 Suppl):61-75
references: 15083871
references: Psychiatry Res. 2008 Nov 30;164(2):132-42
references: 18945599
references: Neuroimage. 2013 Jan 15;65:488-98
references: 23063444
references: Curr Opin Cardiol. 2005 May;20(3):182-8
references: 15861005
references: J Head Trauma Rehabil. 1999 Dec;14(6):602-15
references: 10671706
references: Am J Psychiatry. 2011 Mar;168(3):253-6
references: 21285144
references: Brain Inj. 2008 Aug;22(9):705-14
references: 18698520
references: Am J Epidemiol. 2008 Jan 15;167(2):125-38
references: 17989061
references: J Neurotrauma. 2013 Nov 15;30(22):1852-61
references: 23725058
references: Nat Neurosci. 2008 Jan;11(1):103-7
references: 18066057
references: J Neurotrauma. 2009 Dec;26(12):2207-16
references: 19803786