title: Alcohol dependence with comorbid drug dependence: genetic and phenotypic associations suggest a more severe form of the disorder with stronger genetic contribution to risk.
abstract: BACKGROUND
  Twin data suggest that alcohol dependence comorbid with illicit drug dependence represents a more heritable form of the disorder. In the Collaborative Study on the Genetics of Alcoholism sample, approximately half the alcohol-dependent individuals also meet diagnostic criteria for illicit drug dependence. In this study, we tested for heterogeneity in the association between the muscarinic acetylcholine M2 receptor gene (CHRM2) and alcohol dependence, reported previously in the full sample, among the subgroups of alcohol-dependent individuals with and without comorbid drug dependence.
  
  
  METHODS
  Family-based association tests were conducted separately (a) in individuals with alcohol dependence with comorbid drug dependence (n = 477) and (b) in individuals with alcohol dependence without comorbid drug dependence (n = 433). These subgroups were subsequently compared on other phenotypic characteristics.
  
  
  RESULTS
  The evidence for association between CHRM2 and alcohol dependence came entirely from the subgroup of individuals with comorbid drug dependence. There was no evidence of association with CHRM2 among the alcohol-dependent individuals without drug dependence. Subsequent phenotypic analyses suggest that the subgroup of alcohol-dependent individuals with comorbid drug dependence differ on a number of other phenotypic characteristics, including several measures of the severity of their alcohol problems, personality traits and comorbid psychiatric disorders.
  
  
  CONCLUSIONS
  These analyses provide specific genetic evidence suggesting that alcohol dependence with comorbid drug dependence represents a particularly severe form of the disorder, with higher genetic contribution to vulnerability.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. dickd@psychiatry.wustl.edu
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.forename: Jen C
authors.initials: JC
authors.lastname: Wang
authors.forename: Anthony
authors.initials: A
authors.lastname: Hinrichs
authors.forename: Sarah
authors.initials: S
authors.lastname: Bertelsen
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Bucholz
authors.forename: Marc
authors.initials: M
authors.lastname: Schuckit
authors.forename: John
authors.initials: J
authors.lastname: Kramer
authors.forename: John
authors.initials: J
authors.lastname: Nurnberger
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D043585:Receptor, Muscarinic M2 / Q000235:genetics*; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics*
chemical_list: C487078:CHRM2 protein, human; D043585:Receptor, Muscarinic M2