ArticleEpigenetics2016
BDNF rs6265 methylation and genotype interact on risk for schizophrenia.
Article in Epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 3 of them syntheses that pooled it.
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Who cites it
34 citing papers in PubMed, 3 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Brain-derived neurotrophic factor (BDNF) epigenomic modifications and brain-related phenotypes in humans: A systematic review.Neuroscience and biobehavioral reviews · 2023Pooled it
- DNA methylation and brain structure and function across the life course: A systematic review.Neuroscience and biobehavioral reviews · 2020Pooled it
- Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder: a Systematic Review.Molecular neurobiology · 2018Pooled it
- BDNF-DT and BDNF-AS-DT: novel genes in the BDNF locus.Molecular psychiatry · 2026Article
- Article
- Article
- Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population.Biological psychiatry global open science · 2025Article
- Review
- Brain-derived neurotrophic factor rs6265 (Val66Met) single nucleotide polymorphism as a master modifier of human pathophysiology.Neural regeneration research · 2023Review
- Can epigenetics shine a light on the biological pathways underlying major mental disorders?Psychological medicine · 2022Review
- The stress-vulnerability model on the path to schizophrenia: Interaction between BDNF methylation and schizotypy on the resting-state brain network.Schizophrenia (Heidelberg, Germany) · 2022Article
- Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats.Neuroscience and biobehavioral reviews · 2021Review
- Elevation of DNA Methylation in the Promoter Regions of the Brain-Derived Neurotrophic Factor Gene is Associated with Heroin Addiction.Journal of molecular neuroscience : MN · 2021Article
- AcuteNeurorehabilitation and neural repair · 2021Article
- Glucocorticoid Signaling and Epigenetic Alterations in Stress-Related Disorders.International journal of molecular sciences · 2021Review
- The genetic influence of the brain-derived neurotrophic factor Val66Met polymorphism in chronic low back pain.Advances in rheumatology (London, England) · 2021Article
- BDNF rs6265 Polymorphism and Its Methylation in Patients with Stroke Undergoing Rehabilitation.International journal of molecular sciences · 2020Article
- Association of a Reproducible Epigenetic Risk Profile for Schizophrenia With Brain Methylation and Function.JAMA psychiatry · 2020Article
- Epigenetic Effects on Pediatric Traumatic Brain Injury Recovery (EETR): An Observational, Prospective, Longitudinal Concurrent Cohort Study Protocol.Frontiers in neurology · 2020Article
- Analysis of GWAS-Derived Schizophrenia Genes for Links to Ischemia-Hypoxia Response of the Brain.Frontiers in psychiatry · 2020Article
Corrections and comments
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Authors and funding
28 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val(66)Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes.
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