title: FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students.
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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut.|Department of Neuroscience, University of Connecticut Health Center, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: Richard
authors.initials: R
authors.lastname: Lieberman
authors.affiliation: Department of Psychology, Fairleigh Dickinson University, Teaneck, New Jersey.
authors.forename: Stephen
authors.initials: S
authors.lastname: Armeli
authors.affiliation: Department of Pediatrics and Human Genetics and Alcohol Research Center, Howard University College of Medicine, Washington, District of Columbia.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Scott
authors.affiliation: Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania.|VISN4 MIRECC, Crescenz VAMC, Philadelphia, Pennsylvania.
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.affiliation: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut.|Department of Community Medicine and Health Care, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Howard
authors.initials: H
authors.lastname: Tennen
authors.affiliation: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut.|Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Covault
mesh_terms: D000328:Adult; D000067292:Alcohol Drinking in College / Q000523:psychology*; D000437:Alcoholism / Q000235:genetics; D000483:Alleles; D005260:Female; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008016:Life Change Events; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D057566:Self Report; D013315:Stress, Psychological / Q000235:genetics; D013334:Students / Q000523:psychology; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014947:Wounds and Injuries; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: alcohol; alcohol use disorder; early life stress; gene-environment interaction; polymorphism