title: Exome-wide association study of replicable nonsynonymous variants conferring risk for alcohol dependence.
abstract: OBJECTIVE
  In the present study, we scanned the whole exome in three independent samples to search for replicable risk nonsynonymous (ns) variants (ns single-nucleotide polymorphisms [nsSNPs]) for alcohol dependence.
  
  
  METHODS
  A total of 10,554 subjects in three independent samples were analyzed for association with alcohol dependence, including one European American sample (1,409 cases with alcohol dependence and 1,518 controls), one African American sample (681 cases and 508 controls), and one European Australian sample (a total of 6,438 family subjects with 1,645 alcohol-dependent probands). RNA expression of the risk genes in human, mouse, and rat brains was also explored.
  
  
  RESULTS
  We identified a total of 70 nsSNPs at 65 genes with nominally replicable associations; 22 nsSNPs at 21 genes among them survived corrections for multiple testing in meta-analysis (α = .0007). By incorporating the information from bioinformatics and RNA expression analyses, we identified at least two of the most promising risk genes for alcohol dependence: APOER2 and UBAP2.
  
  
  CONCLUSIONS
  The gene coding for apolipoprotein E receptor 2 (APOER2) and the gene coding for ubiquitin-associated protein-2 (UBAP2) are among the most appropriate for follow-up in human and nonhuman species as contributors to risk for alcohol dependence.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06516, USA. Lingjun.Zuo@yale.edu
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zuo
authors.forename: Laura
authors.initials: L
authors.lastname: Saba
authors.forename: Kesheng
authors.initials: K
authors.lastname: Wang
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zhang
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Boris
authors.initials: B
authors.lastname: Tabakoff
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
mesh_terms: D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D044383:Black People / Q000235:genetics; D019295:Computational Biology; D059472:Exome; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012307:Risk Factors; D013045:Species Specificity; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D026502:LDL-Receptor Related Proteins; C098773:low density lipoprotein receptor-related protein 8; D012313:RNA