title: An extended Swedish national adoption study of alcohol use disorder.
abstract: OBJECTIVE
  Alcohol use disorder (AUD) runs strongly in families. It is unclear to what extent the cross-generational transmission of AUD results from genetic vs environmental factors.
  
  
  OBJECTIVE
  To determine to what extent genetic and environmental factors contribute to the risk for AUD.
  
  
  METHODS
  Follow-up in 8 public data registers of adoptees, their biological and adoptive relatives, and offspring and parents from stepfamilies and not-lived-with families in Sweden. In this cohort study, subtypes of AUD were assessed by latent class analysis. A total of 18,115 adoptees (born 1950-1993) and 171,989 and 107,696 offspring of not-lived-with parents and stepparents, respectively (born 1960-1993).
  
  
  METHODS
  Alcohol use disorder recorded in medical, legal, or pharmacy registry records.
  
  
  RESULTS
  Alcohol use disorder in adoptees was significantly predicted by AUD in biological parents (odds ratio, 1.46; 95% CI, 1.29-1.66) and siblings (odds ratio, 1.94; 95% CI, 1.55-2.44) as well as adoptive parents (odds ratio, 1.40; 95% CI, 1.09-1.80). Genetic and environmental risk indices created from biological and adoptive relatives acted additively on adoptee AUD liability. Results from biological and adoptive relatives were replicated and extended from examinations of, respectively, not-lived-with parents and stepparents. Multivariate models in these families showed that AUD in offspring was significantly predicted by AUD, drug abuse, psychiatric illness, and crime in not-lived-with parents and by AUD, drug abuse, crime, and premature death in stepparents. Latent class analyses of adoptees and offspring of not-lived-with parents with AUDs revealed 3 AUD classes characterized by (1) female preponderance and high rates of psychiatric illness, (2) mild nonrecurrent symptoms, and (3) early-onset recurrence, drug abuse, and crime. These classes had distinct genetic signatures in the patterns of risk for various disorders in their not-lived-with parents and striking differences in the rates of recorded mood disorders.
  
  
  CONCLUSIONS
  Parent-offspring transmission of AUD results from both genetic and environmental factors. Genetic risk for AUD reflects both a specific liability to AUD and to other externalizing disorders. Environmental risk reflects features of both parental psychopathology and other aspects of the rearing environment. Alcohol use disorder is a heterogeneous syndrome and meaningful subtypes emerged from latent class analysis, which were validated by patterns of disorders in biological parents and specific psychiatric comorbidities. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond2Department of Psychiatry, Virginia Commonwealth University, Richmond3Department of Human and Molecular Genetics, Virginia Commonwealth University, Richm.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Ji
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond2Department of Psychiatry, Virginia Commonwealth University, Richmond.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Edwards
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ohlsson
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö, Sweden5Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California.
authors.forename: Jan
authors.initials: J
authors.lastname: Sundquist
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö, Sweden5Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California.
authors.forename: Kristina
authors.initials: K
authors.lastname: Sundquist
mesh_terms: D000300:Adoption; D000328:Adult; D019973:Alcohol-Related Disorders / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D002648:Child; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010290:Parents; D012042:Registries / Q000706:statistics & numerical data*; D012307:Risk Factors; D035781:Siblings; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult