A family study of alcohol dependence: Coaggregation of multiple disorders in relatives of alcohol-dependent probands

John Nurnberger, Ryan Wiegand, Kathleen Bucholz, Sean O'Connor, Eric T. Meyer, Theodore Reich, John Rice, Marc Schuckit, Lucy King, Theodore Petti, Laura Bierut, Anthony L. Hinrichs, Samuel Kuperman, Victor Hesselbrock, Bernice Porjesz

Research output: Contribution to journalArticle

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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. Design: 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.

Original languageEnglish
Pages (from-to)1246-1256
Number of pages11
JournalArchives of General Psychiatry
Volume61
Issue number12
DOIs
StatePublished - Dec 2004

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Alcoholism
Alcohols
Diagnostic and Statistical Manual of Mental Disorders
Substance-Related Disorders
Antisocial Personality Disorder
Opiate Alkaloids
Interviews
Cohort Effect
Panic Disorder
Obsessive-Compulsive Disorder
Alcoholics
Cannabis
Post-Traumatic Stress Disorders
Anxiety Disorders
Hypnotics and Sedatives
Mood Disorders
Cocaine
Tobacco
Medical Records
Psychiatry

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

A family study of alcohol dependence : Coaggregation of multiple disorders in relatives of alcohol-dependent probands. / Nurnberger, John; Wiegand, Ryan; Bucholz, Kathleen; O'Connor, Sean; Meyer, Eric T.; Reich, Theodore; Rice, John; Schuckit, Marc; King, Lucy; Petti, Theodore; Bierut, Laura; Hinrichs, Anthony L.; Kuperman, Samuel; Hesselbrock, Victor; Porjesz, Bernice.

In: Archives of General Psychiatry, Vol. 61, No. 12, 12.2004, p. 1246-1256.

Research output: Contribution to journalArticle

Nurnberger, J, Wiegand, R, Bucholz, K, O'Connor, S, Meyer, ET, Reich, T, Rice, J, Schuckit, M, King, L, Petti, T, Bierut, L, Hinrichs, AL, Kuperman, S, Hesselbrock, V & Porjesz, B 2004, 'A family study of alcohol dependence: Coaggregation of multiple disorders in relatives of alcohol-dependent probands', Archives of General Psychiatry, vol. 61, no. 12, pp. 1246-1256. https://doi.org/10.1001/archpsyc.61.12.1246
Nurnberger, John ; Wiegand, Ryan ; Bucholz, Kathleen ; O'Connor, Sean ; Meyer, Eric T. ; Reich, Theodore ; Rice, John ; Schuckit, Marc ; King, Lucy ; Petti, Theodore ; Bierut, Laura ; Hinrichs, Anthony L. ; Kuperman, Samuel ; Hesselbrock, Victor ; Porjesz, Bernice. / A family study of alcohol dependence : Coaggregation of multiple disorders in relatives of alcohol-dependent probands. In: Archives of General Psychiatry. 2004 ; Vol. 61, No. 12. pp. 1246-1256.
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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. Design: 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.",
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AU - Wiegand, Ryan

AU - Bucholz, Kathleen

AU - O'Connor, Sean

AU - Meyer, Eric T.

AU - Reich, Theodore

AU - Rice, John

AU - Schuckit, Marc

AU - King, Lucy

AU - Petti, Theodore

AU - Bierut, Laura

AU - Hinrichs, Anthony L.

AU - Kuperman, Samuel

AU - Hesselbrock, Victor

AU - Porjesz, Bernice

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N2 - 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. Design: 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.

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