Genotype-expression interactions for BDNF across human brain regions.

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.