title: Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder.
abstract: FKBP5 regulates the cortisol-binding affinity and nuclear translocation of the glucocorticoid receptor. Polymorphisms at the FKBP5 locus have been associated with increased recurrence risk of depressive episodes and rapid response to antidepressant treatment. A recent study showed that FKBP5 genotypes moderated the risk of post-traumatic stress disorder (PTSD) symptoms associated with childhood maltreatment. One thousand one hundred forty-three European Americans (EAs) and 1284 African Americans (AAs) recruited for studies of the genetics of substance dependence were also screened for lifetime PTSD. Four single-nucleotide polymorphisms (SNPs) in FKBP5, rs3800373, rs9296158, rs1360780, and rs9470080, were genotyped on the complete sample. Logistic regression analyses were performed to explore the interactive effect of FKBP5 polymorphisms and childhood adversity on the risk for PTSD. After correction for multiple testing, childhood adversity significantly increased the risk for PTSD. FKBP5 genotypes were not associated with the development of the disorder. In AAs, one of the SNPs, rs9470080, moderated the risk of PTSD that was associated with childhood abuse. Without childhood adverse experiences, participants with the TT genotype of this SNP had the lowest risk for PTSD, whereas they had the highest risk for PTSD after childhood adversity exposure. In addition, in EAs, alcohol dependence was observed to interact with childhood adverse experiences, and also FKBP5 polymorphisms, to increase the risk for PTSD. This study provides further evidence of a gene x environment effect of FKBP5 and childhood abuse on the risk for PTSD in AAs. Further study is required in other populations.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Pingxing
authors.initials: P
authors.lastname: Xie
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: James
authors.initials: J
authors.lastname: Poling
authors.forename: Murray B
authors.initials: MB
authors.lastname: Stein
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Anton
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000328:Adult; D054523:Adult Survivors of Child Abuse; D001741:Black or African American; D000437:Alcoholism / Q000235:genetics / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D013313:Stress Disorders, Post-Traumatic / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D044465:White People; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
references.citation: Biol Psychiatry. 2007 Nov 15;62(10):1080-7
references.pmid: 17662255
references.citation: Am J Psychiatry. 1999 Aug;156(8):1223-9
references.pmid: 10450264
references.citation: Biol Psychiatry. 2008 Jun 15;63(12):1103-10
references.pmid: 18191112
references.citation: Neuroendocrinology. 1995 Oct;62(4):340-7
references.pmid: 8544947
references.citation: Mol Psychiatry. 2005 May;10(5):500-13, 425
references.pmid: 15685253
references.citation: JAMA. 1997 May 7;277(17):1362-8
references.pmid: 9134941
references.citation: Am J Psychiatry. 1999 Apr;156(4):585-8
references.pmid: 10200738
references.citation: Genetics. 2003 Aug;164(4):1567-87
references.pmid: 12930761
references.citation: Nat Neurosci. 2009 Mar;12(3):342-8
references.pmid: 19234457
references.citation: Biometrics. 1986 Mar;42(1):121-30
references.pmid: 3719049
references.citation: Am J Hum Genet. 1999 Jul;65(1):220-8
references.pmid: 10364535
references.citation: Biol Psychiatry. 2003 Oct 1;54(7):710-8
references.pmid: 14512211
references.citation: Acta Psychiatr Scand. 1998 Oct;98(4):328-35
references.pmid: 9821456
references.citation: Am J Psychiatry. 1995 Jul;152(7):982-6
references.pmid: 7793468
references.citation: Genet Epidemiol. 2005 May;28(4):302-12
references.pmid: 15782414
references.citation: Nat Genet. 2004 Dec;36(12):1319-25
references.pmid: 15565110
references.citation: Am J Hum Genet. 2006 May;78(5):759-769
references.pmid: 16642432
references.citation: JAMA. 2008 Mar 19;299(11):1291-305
references.pmid: 18349090
references.citation: Am J Psychiatry. 2007 Apr;164(4):617-21
references.pmid: 17403975
references.citation: Arch Gen Psychiatry. 2009 Nov;66(11):1201-9
references.pmid: 19884608
references.citation: Biol Psychiatry. 2009 Mar 1;65(5):409-16
references.pmid: 19013558
references.citation: J Consult Clin Psychol. 2000 Oct;68(5):782-7
references.pmid: 11068964
references.citation: J Biol Chem. 2002 Feb 15;277(7):4597-600
references.pmid: 11751894
references.citation: Horm Behav. 2006 Nov;50(4):632-9
references.pmid: 16876168
references.citation: Psychol Med. 2004 Nov;34(8):1475-82
references.pmid: 15724878
references.citation: Drug Alcohol Depend. 2007 Nov 2;91(1):85-90
references.pmid: 17590536
references.citation: Am J Public Health. 2001 May;91(5):753-60
references.pmid: 11344883
references.citation: J Biol Chem. 2005 Feb 11;280(6):4609-16
references.pmid: 15591061
references.citation: J Clin Endocrinol Metab. 2003 Jan;88(1):277-84
references.pmid: 12519866
references.citation: Br J Psychiatry. 1993 Aug;163:239-47
references.pmid: 8075917
references.citation: Psychol Med. 1993 Aug;23(3):679-90
references.pmid: 8234575
references.citation: J Trauma Stress. 1994 Jan;7(1):83-93
references.pmid: 8044445
references.citation: Am J Psychiatry. 1996 Feb;153(2):275-7
references.pmid: 8561213
references.citation: Eur Child Adolesc Psychiatry. 2000 Dec;9(4):235-43
references.pmid: 11202098
references.citation: J Affect Disord. 2004 Oct 15;82(2):217-25
references.pmid: 15488250
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5;136B(1):45-52
references.pmid: 15909294
references.citation: Psychoneuroendocrinology. 2002 Jan-Feb;27(1-2):199-220
references.pmid: 11750779
references.citation: Arch Gen Psychiatry. 2005 Jun;62(6):593-602
references.pmid: 15939837
references.citation: Science. 1997 Sep 12;277(5332):1659-62
references.pmid: 9287218
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: Nat Neurosci. 2004 Aug;7(8):847-54
references.pmid: 15220929
references.citation: Biol Psychiatry. 2009 Oct 1;66(7):708-11
references.pmid: 19393990
references.citation: Neuropsychopharmacology. 1998 Apr;18(4):253-62
references.pmid: 9509493
references.citation: Am J Orthopsychiatry. 1996 Jul;66(3):437-48
references.pmid: 8827267
references.citation: Adv Exp Med Biol. 1986;196:81-96
references.pmid: 3012985
references.citation: Am J Psychiatry. 1996 Jul;153(7):929-34
references.pmid: 8659616
references.citation: Drug Alcohol Depend. 2005 Dec 12;80(3):303-12
references.pmid: 15896927
references.citation: Psychoneuroendocrinology. 2008 Jul;33(6):693-710
references.pmid: 18602762
references.citation: Genetics. 2000 Jun;155(2):945-59
references.pmid: 10835412
references.citation: Mol Psychiatry. 2005 Dec;10(12):1058-9
references.pmid: 16088328
references.citation: J Psychiatr Res. 2006 Sep;40(6):550-67
references.pmid: 16214171
references.citation: Biol Psychiatry. 2004 Jun 1;55(11):1110-6
references.pmid: 15158431
references.citation: Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S186-95
references.pmid: 19560279