title: A family study of alcohol dependence: coaggregation of multiple disorders in relatives of alcohol-dependent probands.
abstract: BACKGROUND
  Alcohol dependence tends to aggregate within families. We analyzed data from the family collection of the Collaborative Study on the Genetics of Alcoholism to quantify familial aggregation using several different criterion sets. We also assessed the aggregation of other psychiatric disorders in the same sample to identify areas of possible shared genetic vulnerability.
  
  
  METHODS
  Age-corrected lifetime morbid risk was estimated in adult first-degree relatives of affected probands and control subjects for selected disorders. Diagnostic data were gathered by semistructured interview (the Semi-Structured Assessment for the Genetics of Alcoholism), family history, and medical records. Rates of illness were corrected by validating interview and family history reports against senior clinicians' all sources best estimate diagnoses. Sex, ethnicity, comorbidity, cohort effects, and site of ascertainment were also taken into account.
  
  
  RESULTS
  Including data from 8296 relatives of alcoholic probands and 1654 controls, we report lifetime risk rates of 28.8% and 14.4% for DSM-IV alcohol dependence in relatives of probands and controls, respectively; respective rates were 37.0% and 20.5% for the less stringent DSM-III-R alcohol dependence, 20.9% and 9.7% for any DSM-III-R diagnosis of nonalcohol nonnicotine substance dependence, and 8.1% and 5.2% for antisocial personality disorder. Rates of specific substance dependence were markedly increased in relatives of alcohol-dependent probands for cocaine, marijuana, opiates, sedatives, stimulants, and tobacco. Aggregation was also seen for panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and major depression.
  
  
  CONCLUSIONS
  The risk of alcohol dependence in relatives of probands compared with controls is increased about 2-fold. The aggregation of antisocial personality disorder, drug dependence, anxiety disorders, and mood disorders suggests common mechanisms for these disorders and alcohol dependence within some families. These data suggest new phenotypes for molecular genetic studies and alternative strategies for studying the heterogeneity of alcohol dependence.
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202-4887, USA. jnurnber@iupui.edu
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: Ryan
authors.initials: R
authors.lastname: Wiegand
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bucholz
authors.forename: Sean
authors.initials: S
authors.lastname: O'Connor
authors.forename: Eric T
authors.initials: ET
authors.lastname: Meyer
authors.forename: Theodore
authors.initials: T
authors.lastname: Reich
authors.forename: John
authors.initials: J
authors.lastname: Rice
authors.forename: Marc
authors.initials: M
authors.lastname: Schuckit
authors.forename: Lucy
authors.initials: L
authors.lastname: King
authors.forename: Theodore
authors.initials: T
authors.lastname: Petti
authors.forename: Laura
authors.initials: L
authors.lastname: Bierut
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Hinrichs
authors.forename: Samuel
authors.initials: S
authors.lastname: Kuperman
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D005006:Ethnicity / Q000235:genetics; D005190:Family; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D012306:Risk; D014481:United States / Q000453:epidemiology