Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and its association with select anxiety-related disorders: an updated systematic review and meta-analysis

BACKGROUND: Conflicting results on the association of the Val66Met polymorphism in the BDNF gene with anxiety-related disorders are observed from previous studies and meta-analyses. We performed an updated meta-analysis to obtain more precise estimates and add additional analyses not performed by previous reviews.METHODS: Using combinations of various key terms, articles in PubMed, Google Scholar, and Web of Science, written in English were collected until October 31, 2024. Data were extracted independently by two authors and analyzed using Review Manager 5.4.RESULTS: Fifteen studies that are compliant with the HWE, providing a total of 14,184 participants were included in this meta-analysis after applying predefined inclusion/exclusion criteria based on study design, DSM-based diagnosis, and availability of genotype counts. Most pooled models demonstrated low to moderate heterogeneity with significant associations in the recessive model only. In the subgroup analysis, a significant effect was observed in the PD-uncategorized cohort. The Met/Met genotype demonstrated a suggestive association with increased susceptibility to panic disorder.CONCLUSION: Our updated meta-analysis suggests that the Met/Met genotype of the BDNF Val66Met polymorphism may increase susceptibility to PD under a recessive genetic model; however, this evidence remains preliminary.