title: Confirmation of prior evidence of genetic susceptibility to alcoholism in a genome-wide association study of comorbid alcoholism and bipolar disorder.
abstract: OBJECTIVE
  Alcoholism and affective disorders are both strongly comorbid and heritable. We have investigated the genetic comorbidity between bipolar affective disorder and alcoholism.
  
  
  METHODS
  A genome-wide allelic association study of 506 patients from the University College London bipolar disorder case-control sample and 510 ancestrally matched supernormal controls. One hundred forty-three of the bipolar patients fulfilled the Research Diagnostic Criteria diagnosis of alcoholism. A total of 372 193 single nucleotide polymorphisms (SNPs) were genotyped. Genes previously shown to be associated with alcoholism and addiction phenotypes were then tested for association in the bipolar alcoholic sample using gene-wise permutation tests of all SNPs genotyped within a 50-kb region flanking each gene.
  
  
  RESULTS
  Several central nervous system genes showed significant (P<0.05) gene-wise evidence of association with bipolar alcoholism. The genes implicated, which replicated genes previously shown to be associated with alcoholism were: cadherin 11, collagen type 11 α2, neuromedin U receptor 2, exportin7, and semaphorin-associated protein 5A. The SNPs most strongly implicated in bipolar alcoholism, but, which did not meet conventional genome-wide significance criteria were the insulin-like growth factor-binding protein 7, carboxypeptidase O, cerebellin 2, and the cadherin 12 genes.
  
  
  CONCLUSIONS
  We have confirmed the role of some genes previously shown to be associated with alcoholism in the comorbid bipolar alcoholism subgroup. In this subgroup, bipolar disorder may lower the threshold for the phenotypic expression of these alcoholism susceptibility genes. We also show that some genes may independently increase susceptibility to affective disorder and alcoholism.
authors.affiliation: Department of Mental Health Sciences, University College London, Molecular Psychiatry Laboratory, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Gregory John
authors.initials: GJ
authors.lastname: Lydall
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Bass
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Jacob
authors.initials: J
authors.lastname: Lawrence
authors.forename: Adebayo
authors.initials: A
authors.lastname: Anjorin
authors.forename: Radhika
authors.initials: R
authors.lastname: Kandaswamy
authors.forename: Ana
authors.initials: A
authors.lastname: Pereira
authors.forename: Irene
authors.initials: I
authors.lastname: Guerrini
authors.forename: David
authors.initials: D
authors.lastname: Curtis
authors.forename: Anna E
authors.initials: AE
authors.lastname: Vine
authors.forename: Pamela
authors.initials: P
authors.lastname: Sklar
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Purcell
authors.forename: Hugh Malcolm Douglas
authors.initials: HM
authors.lastname: Gurling
mesh_terms: D000437:Alcoholism / Q000453:epidemiology* / Q000235:genetics*; D001714:Bipolar Disorder / Q000453:epidemiology* / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D015897:Comorbidity; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008131:London / Q000453:epidemiology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D015820:Cadherins; D005819:Genetic Markers; C086960:osteoblast cadherin