Network Analysis of EtOH-related Candidate Genes

Overview

Journal Chem Biodivers

Specialty Biochemistry

Date 2010 May 22

PMID 20491071

Citations 3

Authors

An-Yuan Guo

Jingchun Sun

Peilin Jia

Zhongming Zhao

Affiliations

Soon will be listed here.

Abstract

Recently, we collected many large-scale datasets for alcohol dependence and EtOH response in five organisms and deposited them in our EtOH-related gene resource database (ERGR, http://bioinfo.mc.vanderbilt.edu/ERGR/). Based on multidimensional evidence among these datasets, we prioritized 57 EtOH-related candidate genes. To explore their biological roles, and the molecular mechanisms of EtOH response and alcohol dependence, we examined the features of these genes by the Gene Ontology (GO) term-enrichment test and network/pathway analysis. Our analysis revealed that these candidate genes were highly enriched in alcohol dependence/alcoholism and highly expressed in brain or liver tissues. All the significantly enriched GO terms were related to neurotransmitter systems or EtOH metabolic processes. Using the Ingenuity Pathway Analysis system, we found that these genes were involved in networks of neurological disease, cardiovascular disease, inflammatory response, and small molecular metabolism. Many key genes in signaling pathways were in the central position of these networks. Furthermore, our protein-protein interaction (PPI) network analysis suggested some novel candidate genes which also had evidence in the ERGR database. This study demonstrated that our candidate gene selection is effective and our network/pathway analysis is useful for uncovering the molecular mechanisms of EtOH response and alcohol dependence. This approach can be applied to study the features of candidate genes of other complex traits/phenotypes.

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References

Guo A, Webb B, Miles M, Zimmerman M, Kendler K, Zhao Z . ERGR: An ethanol-related gene resource. Nucleic Acids Res. 2008; 37(Database issue):D840-5. PMC: 2686553. DOI: 10.1093/nar/gkn816. View

Pandey S, Zhang H, Roy A, Xu T . Deficits in amygdaloid cAMP-responsive element-binding protein signaling play a role in genetic predisposition to anxiety and alcoholism. J Clin Invest. 2005; 115(10):2762-73. PMC: 1236671. DOI: 10.1172/JCI24381. View

Schumann G, Rujescu D, Kissling C, Soyka M, Dahmen N, Preuss U . Analysis of genetic variations of protein tyrosine kinase fyn and their association with alcohol dependence in two independent cohorts. Biol Psychiatry. 2003; 54(12):1422-6. DOI: 10.1016/s0006-3223(03)00635-8. View

Lewohl J, Wang L, Miles M, Zhang L, Dodd P, Harris R . Gene expression in human alcoholism: microarray analysis of frontal cortex. Alcohol Clin Exp Res. 2001; 24(12):1873-82. View

Ren J, Wold L . Mechanisms of alcoholic heart disease. Ther Adv Cardiovasc Dis. 2009; 2(6):497-506. DOI: 10.1177/1753944708095137. View

Kohnke M . Approach to the genetics of alcoholism: a review based on pathophysiology. Biochem Pharmacol. 2007; 75(1):160-77. DOI: 10.1016/j.bcp.2007.06.021. View

Su A, Wiltshire T, Batalov S, Lapp H, Ching K, Block D . A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci U S A. 2004; 101(16):6062-7. PMC: 395923. DOI: 10.1073/pnas.0400782101. View

Szabo G, Mandrekar P . A recent perspective on alcohol, immunity, and host defense. Alcohol Clin Exp Res. 2008; 33(2):220-32. PMC: 3787826. DOI: 10.1111/j.1530-0277.2008.00842.x. View

Dennis Jr G, Sherman B, Hosack D, Yang J, Gao W, Lane H . DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003; 4(5):P3. View

10.

Ishiguro H, Saito T, Shibuya H, Toru M, Arinami T . Mutation and association analysis of the Fyn kinase gene with alcoholism and schizophrenia. Am J Med Genet. 2000; 96(6):716-20. View

11.

Sokolov B, Jiang L, Trivedi N, Aston C . Transcription profiling reveals mitochondrial, ubiquitin and signaling systems abnormalities in postmortem brains from subjects with a history of alcohol abuse or dependence. J Neurosci Res. 2003; 72(6):756-67. DOI: 10.1002/jnr.10631. View

12.

Schumann G, Spanagel R, Mann K . Candidate genes for alcohol dependence: animal studies. Alcohol Clin Exp Res. 2003; 27(5):880-8. DOI: 10.1097/01.ALC.0000065437.18136.86. View

13.

Guo A, Sun J, Riley B, Thiselton D, Kendler K, Zhao Z . The dystrobrevin-binding protein 1 gene: features and networks. Mol Psychiatry. 2008; 14(1):18-29. PMC: 2859304. DOI: 10.1038/mp.2008.88. View

14.

Liu J, Lewohl J, Harris R, Iyer V, Dodd P, Randall P . Patterns of gene expression in the frontal cortex discriminate alcoholic from nonalcoholic individuals. Neuropsychopharmacology. 2005; 31(7):1574-82. DOI: 10.1038/sj.npp.1300947. View

15.

Zhai H, Li Y, Wang X, Lu L . Drug-induced alterations in the extracellular signal-regulated kinase (ERK) signalling pathway: implications for reinforcement and reinstatement. Cell Mol Neurobiol. 2007; 28(2):157-72. PMC: 11515050. DOI: 10.1007/s10571-007-9240-3. View

16.

Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita K, Itoh M, Kawashima S . From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res. 2005; 34(Database issue):D354-7. PMC: 1347464. DOI: 10.1093/nar/gkj102. View

17.

Pastor I, Laso F, Ines S, Marcos M, Gonzalez-Sarmiento R . Genetic association between -93A/G polymorphism in the Fyn kinase gene and alcohol dependence in Spanish men. Eur Psychiatry. 2008; 24(3):191-4. DOI: 10.1016/j.eurpsy.2008.08.007. View

18.

Quickfall J, El-Guebaly N . Genetics and alcoholism: how close are we to potential clinical applications?. Can J Psychiatry. 2006; 51(7):461-7. DOI: 10.1177/070674370605100708. View

19.

Takashima Y, Kokaze A, Matsunaga N, Yoshida M, Sekiguchi K, Sekine Y . Relations of blood pressure to angiotensinogen gene T174M polymorphism and alcohol intake. J Physiol Anthropol Appl Human Sci. 2003; 22(4):187-94. DOI: 10.2114/jpa.22.187. View

20.

Wand G . The anxious amygdala: CREB signaling and predisposition to anxiety and alcoholism. J Clin Invest. 2005; 115(10):2697-9. PMC: 1236699. DOI: 10.1172/JCI26436. View