title: Multi-species data integration and gene ranking enrich significant results in an alcoholism genome-wide association study.
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.
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: An-Yuan
authors.initials: AY
authors.lastname: Guo
authors.forename: Edwin J C G
authors.initials: EJ
authors.lastname: van den Oord
authors.forename: Fazil
authors.initials: F
authors.lastname: Aliev
authors.forename: Peilin
authors.initials: P
authors.lastname: Jia
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Brien P
authors.initials: BP
authors.lastname: Riley
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: Jill C
authors.initials: JC
authors.lastname: Bettinger
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Davies
authors.forename: Michael S
authors.initials: MS
authors.lastname: Grotewiel
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schuckit
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.forename: John
authors.initials: J
authors.lastname: Kramer
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Webb
authors.forename: Michael F
authors.initials: MF
authors.lastname: Miles
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics; D019295:Computational Biology; D004330:Drosophila / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008040:Genetic Linkage; D016678:Genome; D055106:Genome-Wide Association Study; D006801:Humans; D051379:Mice; D020641:Polymorphism, Single Nucleotide
chemical_list: D000438:Alcohols