Single-nucleotide polymorphism in the human TIA1 gene interacts with stressful life events to predict the development of pathological anxiety symptoms in a Swedish population

Abstract

Background: The TIA1 gene encodes a prion-related RNA-binding protein that regulates stress-dependent synaptic plasticity and fear memory in mice. It is unknown whether genetic variation in human TIA1 is associated with differences in stress- and fear-related behavior in people.

Methods: A longitudinal, population-based survey was conducted in Sweden to collect information on demographics, socioeconomic status, exposure to stressful life events and psychiatric symptoms. DNA samples were obtained from study participants to allow genotyping of single-nucleotide polymorphisms in the human TIA1 locus.

Results: We identified a single-nucleotide polymorphism in the human TIA1 gene that interacts with exposure to previous-year stressful life events to predict the development of pathological anxiety symptoms in a non-clinical cohort.

Limitations: Sample population is limited in both size and scope, and we did not perform functional analysis of allelic variants of TIA1.

Conclusions: TIA1 may represent a susceptibility locus for stress-dependent psychopathology. These studies support an evolutionarily conserved role of TIA1 in the mammalian brain, and may provide molecular and genetic insight into the development of stress-related psychiatric conditions such as PTSD and anxiety.

Keywords: Anxiety; Gene-environment interaction; Genetic association; Stress; Stress vulnerability; TIA1.