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.

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

Figure 1. Interactive effect of FKBP5 rs1360780 and early life trauma in predicting heavy drinking

Daily self-reports of alcohol consumption in a diverse sample of 1845 college students revealed no significant effect of early life trauma on the probability of heavy drinking in carriers of the FKBP5 rs1360780*T-allele (B = −0.23, SE = 0.14, p = 0.51, OR = 1.25). In contrast, a significant effect of early life trauma on the probability of heavy drinking was observed in FKBP5 rs1360780*C/C genotype individuals (B = −0.29, SE = 0.15, p = 0.003, OR = 0.747). The depicted probability of heavy drinking were calculated with the levels for covariates held at their mean. Number of participants within each group is depicted in each bar. (** p < 0.01, NS = not significant).