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.
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.
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.
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.