Biomics

Anxiety represents a complex psychobiological phenotype whose development is determined by the interaction of genetic and environmental factors. The present study aimed to examine associations between polymorphisms in the NRXN1, HTR2A, and BDNF genes and levels of state and trait anxiety, as well as to evaluate gene–environment (GхE) interactions in a student cohort. The study included 1,011 mentally healthy university students from the Republic of Bashkortostan aged 17-21 years. State and trait anxiety levels were assessed using the Russian version of the State–Trait Anxiety Inventory (STAI). Genotyping of NRXN1 (rs1045881, rs4971648), HTR2A (rs6311), and BDNF (rs6265, rs7124442) polymorphisms were performed using KASP-PCR. Women exhibited significantly higher levels of both state and trait anxiety. No significant differences in anxiety levels were observed between ethnic groups. No main genetic effects were detected for NRXN1 or HTR2A polymorphisms. In contrast, carriage of the BDNF rs6265*A (Met) allele was associated with lower trait anxiety, whereas the T allele of rs7124442 was associated with higher state anxiety. G×E analysis revealed an inversion of BDNF polymorphism effects depending on prior COVID-19 infection, as well as a moderating role of family-related factors for the NRXN1 rs4971648 polymorphism. These findings support the context-dependent nature of genetic effects and underscore the importance of integrative approaches in anxiety research.

anxiety, gene–environment interactions, NRXN1, BDNF, HTR2A, COVID-19

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