The Val66Met polymorphism of the BDNF gene in anorexia nervosa: new data and a meta-analysis

Abstract

Objectives: The Val66Met polymorphism (rs6265) of the BDNF gene is a non-synonymous polymorphism, previously associated with anorexia nervosa (AN).

Methods: We genotyped rs6265 in 235 patients with AN and 643 controls. Furthermore, we performed a systematic review of all case-control and family-based studies testing this SNP in AN, and combined the results in a meta-analysis.

Results: The results of the case-control study were non-significant. For the meta-analysis, nine studies were identified (ncases = 2,767; ncontrols = 3,322, ntrios = 53) and included. Primarily, the analyses indicated an association with OR of 1.11 (P = 0.024) in the allelic contrast, and OR of 1.14 (P = 0.025) for the dominant effect of the Met allele. However, additional analyses revealed that the first published study (from those included in the meta-analysis) overly influenced the pooled effect size (possibly due to a phenomenon known as a winner's curse). When this case-control study was replaced by a trio study (ntrios = 293) performed on a largely overlapping sample, the effect size became smaller and non-significant, both for the allelic contrast (OR = 1.07, P = 0.156) and the dominant effect (OR = 1.07, P = 0.319). The quality of included studies was good and there was no significant heterogeneity across the effect sizes.

Conclusions: Our analyses indicate that the BDNF Val66Met variant is not associated with AN at detectable levels.