PUBLICATION
Candidate Risk Genes for Bipolar Disorder are Highly Conserved during Evolution and Highly Interconnected
- Authors
- Franklin, C., Dwyer, D.S.
- ID
- ZDB-PUB-201002-120
- Date
- 2020
- Source
- Bipolar disorders 23(4): 400-408 (Journal)
- Registered Authors
- Keywords
- co-morbidity, evolutionary conservation, gene interactions, synteny
- MeSH Terms
-
- Animals
- Bipolar Disorder*/genetics
- Caenorhabditis elegans
- Humans
- Phenotype
- Zebrafish
- PubMed
- 32959503 Full text @ Bipolar Disord
Citation
Franklin, C., Dwyer, D.S. (2020) Candidate Risk Genes for Bipolar Disorder are Highly Conserved during Evolution and Highly Interconnected. Bipolar disorders. 23(4):400-408.
Abstract
Objectives Bipolar disorder (BPD) is a highly heritable psychiatric disorder whose genetic complexity and pathogenetic mechanisms are still being unraveled. The main goal of this work was to characterize BPD risk-gene candidates (identified by Nurnberger et al., JAMA Psychiatry 71:657, 2014 and Stahl et al., Nat. Genet. 51:793, 2019) with respect to their evolutionary conservation, associated phenotypes and extent of gene-gene interactions.
Methods Database searches and BLAST were used to identify homologous counterparts of human BPD risk genes in C. elegans, zebrafish and Drosophila. Phenotypes associated with the C. elegans genes were annotated and searched. With GeneMANIA, we characterized and quantified gene-gene interactions among members of the BPD gene set in comparison to randomly chosen gene sets of the same size.
Results BPD risk genes are highly conserved across species and are enriched for essential genes and genes associated with lethality and altered life span. They are significantly more interactive with each other in comparison to random genes. We identified syntenic blocks of risk genes, which provided potential insights into molecular pathways and co-morbidities associated with BPD including coronary disease, obesity and decreased life expectancy.
Conclusions BPD risk genes appear to be special in terms of their degree of conservation, interconnectedness and pleiotropic effects that extend beyond a role in brain function. Key hub genes or pleiotropic regulatory components may represent attractive targets for future drug discovery.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping