Analysis of the effects of depression associated polymorphisms on the activity of the BICC1 promoter in amygdala neurones

S. Davidson, L. Shanley, P. Cowie, M. Lear, P. McGuffin, J. P Quinn, P. Barrett, A. MacKenzie

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Abstract

The Bicaudal C Homolog 1 (BICC1) gene, which encodes an RNA binding protein, has been identified by genome wide association studies (GWAS) as a candidate gene associated with major depressive disorder (MDD). We explored the hypothesis that MDD associated single-nucleotide polymorphisms (SNPs) affected the ability of cis-regulatory elements within intron 3 of the BICC1 gene to modulate the activity of the BICC1 promoter region. We initially established that the BICC1 promoter drove BICC1 mRNA expression in amygdala, hippocampus and hypothalamus. Intriguingly, we provide evidence that MDD associated polymorphisms alter the ability of the BICC1 promoter to respond to PKA signalling within amygdala neurones. Considering the known role of amygdala PKA pathways in fear learning and mood these observations suggest a possible mechanism through which allelic changes in the regulation of the BICC1 gene in amygdala neurones may contribute to mood disorders. Our findings also suggest a novel direction for the identification of novel drug targets and the design of future personalised therapeutics.

Original languageEnglish
Pages (from-to)366-374
Number of pages9
JournalThe Pharmacogenomics Journal
Volume16
Issue number4
Early online date6 Oct 2015
DOIs
Publication statusPublished - Aug 2016

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Amygdala
Major Depressive Disorder
Depression
Neurons
Aptitude
Genes
RNA-Binding Proteins
Genome-Wide Association Study
Drug Design
Mood Disorders
Genetic Promoter Regions
Introns
Hypothalamus
Fear
Single Nucleotide Polymorphism
Hippocampus
Learning
Messenger RNA
Therapeutics

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Analysis of the effects of depression associated polymorphisms on the activity of the BICC1 promoter in amygdala neurones. / Davidson, S.; Shanley, L.; Cowie, P.; Lear, M.; McGuffin, P.; Quinn, J. P; Barrett, P.; MacKenzie, A.

In: The Pharmacogenomics Journal, Vol. 16, No. 4, 08.2016, p. 366-374.

Research output: Contribution to journalArticle

Davidson, S. ; Shanley, L. ; Cowie, P. ; Lear, M. ; McGuffin, P. ; Quinn, J. P ; Barrett, P. ; MacKenzie, A. / Analysis of the effects of depression associated polymorphisms on the activity of the BICC1 promoter in amygdala neurones. In: The Pharmacogenomics Journal. 2016 ; Vol. 16, No. 4. pp. 366-374.
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abstract = "The Bicaudal C Homolog 1 (BICC1) gene, which encodes an RNA binding protein, has been identified by genome wide association studies (GWAS) as a candidate gene associated with major depressive disorder (MDD). We explored the hypothesis that MDD associated single-nucleotide polymorphisms (SNPs) affected the ability of cis-regulatory elements within intron 3 of the BICC1 gene to modulate the activity of the BICC1 promoter region. We initially established that the BICC1 promoter drove BICC1 mRNA expression in amygdala, hippocampus and hypothalamus. Intriguingly, we provide evidence that MDD associated polymorphisms alter the ability of the BICC1 promoter to respond to PKA signalling within amygdala neurones. Considering the known role of amygdala PKA pathways in fear learning and mood these observations suggest a possible mechanism through which allelic changes in the regulation of the BICC1 gene in amygdala neurones may contribute to mood disorders. Our findings also suggest a novel direction for the identification of novel drug targets and the design of future personalised therapeutics.",
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