Clinical studies have implicated FK506 binding protein 51 (FKBP5), a co-chaperone of the glucocorticoid receptor (GR), in stress-related disorders. It is known that FKBP5 alters GR complex affinity for cortisol and decreases overall GR signaling.
Human genetic studies indicate that interactions between FKBP5 single-nucleotide polymorphisms (SNPs) and trauma/adversity (eg, emotional neglect or physical abuse) during early childhood period predict the onset of adulthood psychiatric disorders such as depression and posttraumatic stress disorder (PTSD).
Findings of a new study, published in the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, extend the current knowledge on the previously established association between FKBP5 SNPs and childhood adversity, and indicate that early life trauma interacts with FKBP5 genotype to predict heavy alcohol consumption in young adult college students.
Alcohol-attributable mortality is the third leading cause of preventable death in the United States, according to the Centers for Disease Control and Prevention (CDC). Available genetic data [genome-wide association studies (GWAS)] indicate that the heritability of alcohol use disorder (AUD) in humans is approximately 50%.
In the present study, researchers recruited 1 845 students (54% female) to examine interactions between self-reported childhood adversity and the common SNP rs1360780 of the FKBP5. “Examining a sample of college students who regularly use alcohol offers the potential to distinguish between a protective versus risk effect of the rs1360780 polymorphism in the setting of prior life trauma, since a basal level of alcohol consumption in this sample is expected,” the authors noted.
DNA was extracted from saliva samples, and the FKBP5 SNP rs1360780 was genotyped. The overall sample genotype frequencies were as follows: [two copies of the “C” allele (CC = 0.449); one copy of each allele (CT = 0.444); and, (two copies of the “T” allele (TT=0.106) with a minor T-allele frequency of 0.33].
Alcohol use was measured every day (self-reported consumption), and the number of drinks consumed was summed and then converted into a binary indicator of heavy drinking (ie, 4+ drinks for women, and 5+ drinks for men). Early life trauma was measured using the Traumatic Events Screening Inventory (TESI) for adults, and the investigators created a binary variable of either 0 or 1 traumatic event before age 6, since relatively few (6%) participants reported more than one traumatic event during that time period.
Although there was “no main effect of FKBP5 rs1360780 genotype on the probability of heavy drinking,” the researchers found a “significant interaction effect of FKBP5 genotype and early life trauma on the probability of heavy drinking.” More specifically, findings indicate that participants with two copies of the “C” allele (FKBP5 rs1360780 C/C) who reported early life trauma had a lower frequency of heavy drinking, compared with the frequency of heavy drinking among rs1360780 T-allele carriers. The frequency of heavy drinking among T-allele carriers exposed to early life trauma, however, was not significantly different when compared with the frequency of heavy drinking in T-allele carriers who were not exposed to early life trauma.
Thus, according to the authors, “individuals with the FKBP5 rs1360780 C/C genotype who experience early adversity may be protected from heavy alcohol drinking behavior as young adults.” These findings are in line with previous reports that indicate that the FKBP5 rs1360780 C/C genotype confers greater protection against adulthood PTSD and depression in young adults with a history of early childhood trauma.
Lieberman R, Armeli S, Scott DM, et al. FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students. Am J Med Genet B Neuropsychiatr Genet. 2016. doi: 10.1002/ajmg.b.32460. [Epub ahead of print]