Genotype-expression interactions for BDNF across human brain regions

Abstract

Background Genetic variations in brain-derived neurotrophic factor (BDNF) are associated with various psychiatric disorders including depression, obsessive-compulsive disorder, substance use disorders, and schizophrenia; altered gene expression triggered by these genetic variants may serve to create these phenotypes. But genotype-expression interactions for this gene have not been well-studied across brain regions relevant for psychiatric disorders. Results At false discovery rate (FDR) of 10% (q < 0.1), a total of 61 SNPs were associated with BDNF expression in cerebellum (n = 209), 55 SNPs in cortex (n = 205), 48 SNPs in nucleus accumbens (n = 202), 47 SNPs in caudate (n = 194), and 58 SNPs in cerebellar hemisphere (n = 175). We identified a set of 30 SNPs in 2 haplotype blocks that were associated with alterations in expression for each of these 5 regions. The first haplotype block included variants associated in the literature with panic disorders (rs16917204), addiction (rs11030104), bipolar disorder (rs16917237/rs2049045), and obsessive-compulsive disorder (rs6265). Likewise, variants in the second haplotype block have been previously associated with disorders such as nicotine addiction, major depressive disorder (rs988748), and epilepsy (rs6484320/rs7103411). Conclusions This work supports the association of variants within BDNF for expression changes in these key brain regions that may contribute to common behavioral phenotypes for disorders of compulsion, impulsivity, and addiction. These SNPs should be further investigated as possible therapeutic and diagnostic targets to aid in management of these and other psychiatric disorders.

Proteo-transcriptomic analysis reveals brain-region-specific gene and biomarker expression in post-mortem neural tissue of Alzheimer’s patients

“…Analyses determined that there was a significant difference between groups of different brain regions in BDNF expression levels, consistent with prior reports 8 . BDNF is a vital neurotrophin responsible for regulating neural plasticity, growth, differentiation, and synaptic strength 9 .…”

“…Brain-derived neurotrophic factor, or BDNF, plays an important role in neuroplasticity, neurogenesis, learning, and long-term memory 9 . A decrease in BDNF levels has been associated with several neurodegenerative disorders including Alzheimer’s disease 8 . APOE4 is an allele of the apolipoprotein E gene.…”

“…However, a previous study reported that APOE4 allele carriers showed lower levels of BDNF 15 . This is logical as APOE4 carriers have shown to be more susceptible to developing Alzheimer’s disease 1 , and reduced levels of neurotrophins, such as BDNF, have been strongly associated with AD symptoms and pathogenesis 8 . The weak correlation found between APOE4 allele presence and BDNF levels in our study is likely due to the relatively small sample size of the original Aging, Dementia, and TBI study 4 .…”

The Role of Brain-Derived Neurotrophic Factor in Immune-Related Diseases: A Narrative Review

“…They are substances responsible for the development, growth, and overall functioning of neurons; however, they might also modulate neurotransmitter release at presynaptic terminals [ 18 , 19 ]. One of them is brain-derived neurotrophic factor (BDNF), a nerve growth factor commonly expressed in the central nervous system; the intensity of expression varies depending on the region as well as concomitant pathologies, e.g., psychiatric disorders or aging [ 20 , 21 ]. BDNF fulfils numerous functions, contributing to neuro- and gliogenesis and regulating synaptic plasticity, as well as inhibitory and excitatory transmission [ 21 , 22 ].…”

BDNF Therapeutic Mechanisms in Neuropsychiatric Disorders

“…The expression level of BDNF is, at least partly, activity-dependent, as observed in the human cerebral cortex [ 11 ] as well as murine models, such that enriched environmental experiences and sensory stimulation increase BDNF levels in primary sensory cortices and hippocampus [ 12 , 13 ], while sensory deprivation leads to the opposite [ 14 , 15 ]. However, the synthesis and release of BDNF is heavily regulated by various physiological and pathological stimuli [ 3 , 16 ] and show significant genotype-expression interactions [ 17 ] and polymorphic variations [ 18 ]. In addition, altered central and peripheral plasma BDNF levels are significantly associated with numerous brain pathologies and, thus, have been described as biomarkers of a wide array of neuropsychiatric disorders [ 19 , 20 ].…”