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Am J Med Genet B Neuropsychiatr Genet. 2016 Sep;171(6):879-87. doi: 10.1002/ajmg.b.32460. Epub 2016 May 19.

FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students.

Author information

1
Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut.
2
Department of Neuroscience, University of Connecticut Health Center, University of Connecticut School of Medicine, Farmington, Connecticut.
3
Department of Psychology, Fairleigh Dickinson University, Teaneck, New Jersey.
4
Department of Pediatrics and Human Genetics and Alcohol Research Center, Howard University College of Medicine, Washington, District of Columbia.
5
Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania.
6
VISN4 MIRECC, Crescenz VAMC, Philadelphia, Pennsylvania.
7
Department of Community Medicine and Health Care, University of Connecticut Health Center, Farmington, Connecticut.
8
Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut.

Abstract

Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self-reported early life trauma, past-year life stress, past-year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780*T-allele carriers, rs1360780*C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past-year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking.

KEYWORDS:

alcohol; alcohol use disorder; early life stress; gene-environment interaction; polymorphism

PMID:
27196697
PMCID:
PMC5045724
DOI:
10.1002/ajmg.b.32460
[Indexed for MEDLINE]
Free PMC Article

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