BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction

J Affect Disord. 2018 Feb:227:226-235. doi: 10.1016/j.jad.2017.10.024. Epub 2017 Oct 16.


Background: Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression.

Methods: Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases.

Results: The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03).

Limitations: The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was.

Conclusions: We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect.

Keywords: BDNF; Childhood adversity; Depression; Gene-environment interaction; Stressful life events.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain-Derived Neurotrophic Factor / genetics*
  • Depression / genetics*
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease*
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Stress, Psychological / genetics*


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human