No association of genetic variants in BDNF with major depression: A meta‐ and gene‐based analysis

Abstract

Major depressive disorder (MDD) is a complex psychiatric condition with strong genetic predisposition. The association of MDD with genetic polymorphisms, such as Val66Met (rs6265), in the brain derived neurotrophic factor (BDNF), have been reported in many studies and the results were conflicting. In this study, we performed a systematic literature search and conducted random-effects meta-analysis to evaluate genetic variants in BDNF with MDD. A gene-based analysis was also conducted to investigate the cumulative effects of genetic polymorphisms in BDNF. A total of 28 studies from 26 published articles were included in our analysis. Meta-analysis yielded an estimated odds ratio (OR) of 0.96 (95% CI: 0.89–1.05; P= 0.402) for Val66Met (rs6265), 0.83 (95% CI: 0.67–1.04; P= 0.103) for 11757C/G, 1.16 (95% CI: 0.74–1.82; P= 0.527) for 270T/C, 1.03 (95% CI: 0.18–5.75; P= 0.974) for 712A/G and 0.98 (95% CI: 0.85–1.14; P= 0.831) for rs988748. The gene-based analysis indicated that BDNF is not associated with MDD (P>0.21). Our updated meta- and novel gene-based analyses provide no evidence of the association of BDNF with major depression.

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…However, available data do not support a significant effect of rs6265 on MDD susceptibility, as indicated by meta-analyses (Gratacos et al 2007;Gyekis et al 2013) that also provided negative findings for other BDNF SNPs (11757C/G, 270T/C, 712A/G and rs988748). Conversely, the rs6265 Met allele was demonstrated to moderate the relationship between life stress and depression (Hosang et al 2014;Gutierrez et al 2015).…”

Single-Nucleotide Polymorphism of the FKBP5 Gene and Childhood Maltreatment as Predictors of Structural Changes in Brain Areas Involved in Emotional Processing in Depression

“…Mediators of neuronal plasticity have been studied as well, such as the brain derived neurotrophic factor (BDNF) (Arlt et al, 2013;Lavebratt et al, 2010) and BicC family RNA binding protein 1 (BICC1) (Bermingham et al, 2012) genes. However, all genome-wide association analyses that have been performed have so far found inconclusive results regarding the association between SNPs in all these genes and MDD, suggesting that environmental factors may be crucial for developing the disease regardless of genetic vulnerability (Gyekis et al, 2013;Bosker et al, 2011;Clarke et al, 2010;Cohen-Woods et al, 2013).…”

BDNF Val66Met polymorphism and plasma levels in Chinese Han population with obsessive-compulsive disorder and generalized anxiety disorder

“…However the following studies showed inconsistent results (Alonso et al, 2008;Wendland et al, 2007;Zai et al, 2005), some even said that Met66 was a risk allele for OCD (Hemmings et al, 2008;Hemmings et al, 2013). There have been already several meta-analysis in different kinds of mental disorders, such as depression, bipolar disorders, schizophrenia, anorexia nervosa and drug abuse (Brandys et al, 2013;Gonzalez-Castro et al, 2014;Gyekis et al, 2013;Harrisberger et al, 2014;Kanazawa et al, 2007;Verhagen et al, 2010). Most of them found no association between disease and Val66Met.…”