Multi-species data integration and gene ranking enrich significant results in an alcoholism genome-wide association study
Year: 2012
Type: article
Abstract: BACKGROUND: A variety of species and experimental designs have been used to study genetic influences on alcohol dependence, ethanol response, and related traits. Integration of these heterogeneous data can be used to produce a ranked target gene list for additional investigation. RESULTS: In this study, we performed a unique multi-species evidence-based data integration using three microarray experiments in mice or humans that generated an initial alcohol dependence (AD) related genes list, human linkage and association results, and gene sets implicated in C. elegans and Drosophila. We then used permutation and false discovery rate (FDR) analyses on the genome-wide association studies (GWAS) dataset from the Collaborative Study on the Genetics of Alcoholism (COGA) to evaluate the ranking results and weighting matrices. We found one weighting score matrix could increase FDR based q-values for a list of 47 genes with a score greater than 2. Our follow up functional enrichment tests revealed these genes were primarily involved in brain responses to ethanol and neural adaptations occurring with alcoholism. CONCLUSIONS: These results, along with our experimental validation of specific genes in mice, C. elegans and Drosophila, suggest that a cross-species evidence-based approach is useful to identify candidate genes contributing to alcoholism.
Source: BMC Genomics
Authors: Zhongming Zhao, An-Yuan Guo, Edwin JCG van den Oord, Fazil Aliev, Peilin Jia, Howard J Edenberg, Brien P Riley, Danielle M Dick, Jill C Bettinger, Andrew G Davies, Michael S Grotewiel, Marc A Schuckit, Arpana Agrawal, John Kramer, John I Nurnberger, Kenneth S Kendler, Bradley T Webb, Michael F Miles
Institutions: Vanderbilt University, Huazhong University of Science and Technology, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, Indiana University Indianapolis, Indiana University School of Medicine, University of California San Diego, Washington University in St. Louis, University of Iowa
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,090
Awards: G1083756078, Generation of Ethanol Response Gene Resource by Large-Scale Data Integration, G2481876672, G3328282985, G4937580407, Multidisciplinary Approaches to the Genetics of Alcohol-Related Behaviors, JH/CIDR Genotyping for Genome-Wide Association Studies, G5960324223, Cross Species Characterization of Gene Networks in Acute Responses to Ethanol, G7577664313, G8267674335, G858805679
OpenAlex ID: W2159488115