Using dimensional models of externalizing psychopathology to aid in gene identification

Danielle M. Dick, Fazil Aliev, Jen C. Wang, Richard A. Grucza, Marc Schuckit, Samuel Kuperman, John Kramer, Anthony Hinrichs, Sarah Bertelsen, John P. Budde, Victor Hesselbrock, Bernice Porjesz, Howard Edenberg, Laura Jean Bierut, Alison Goate

Research output: Contribution to journalArticle

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Abstract

Context: Twin studies provide compelling evidence that alcohol and drug dependence, childhood conduct disorder, adult antisocial behavior, and disinhibitory personality traits share an underlying genetic liability that contributes to a spectrum of externalizing behaviors. However, this information has not been widely used in gene identification efforts, which have focused on specific disorders diagnosed using traditional psychiatric classification systems. Objective: To test the utility of using a multivariate externalizing phenotype in (1) linkage analyses and (2) association analyses to identify genes that contribute broadly to a spectrum of externalizing disorders. Design: Data were analyzed from the Collaborative Study on the Genetics of Alcoholism. Linkage analyses were conducted using data from a genome-wide 10-cM microsatellite scan. Association analyses were conducted on 27 single-nucleotide polymorphisms genotyped across a candidate gene, the muscarinic acetylcholine receptor M2 gene (CHRM2). Setting: Six centers across the United States. Other Participants: Approximately 2300 individuals from 262 families. Main Outcome Measures: Lifetime symptom counts of alcohol dependence, illicit drug dependence, childhood conduct disorder, and adult antisocial personality disorder and novelty seeking, sensation seeking, and general externalizing component scores consisting of a composite of the previous 6 variables. Results: Principal component analyses indicated that the 6 individual variables loaded on a single externalizing factor. Linkage analyses using the resultant component scores identified a region on chromosome 7 consistent with a gene that broadly predisposes individuals to externalizing behavior. Association analyses of a candidate gene, CHRM2, previously of interest in the Collaborative Study on the Genetics of Alcoholism, suggest that it is involved in a general externalizing phenotype. Conclusions: Broader conceptualizations of psychiatric disorders, such as studying a spectrum of externalizing psychopathology, may aid in identifying susceptibility genes and understanding the pathways through which genetic factors affect vulnerability for a variety of poor outcomes.

Original languageEnglish
Pages (from-to)310-318
Number of pages9
JournalArchives of General Psychiatry
Volume65
Issue number3
StatePublished - Mar 2008

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Psychopathology
Alcoholism
Genes
Conduct Disorder
Substance-Related Disorders
Psychiatry
Muscarinic M2 Receptors
Phenotype
Antisocial Personality Disorder
Twin Studies
Chromosomes, Human, Pair 7
Genetic Association Studies
Street Drugs
Muscarinic Receptors
Principal Component Analysis
Microsatellite Repeats
Single Nucleotide Polymorphism
Personality
Outcome Assessment (Health Care)
Genome

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Dick, D. M., Aliev, F., Wang, J. C., Grucza, R. A., Schuckit, M., Kuperman, S., ... Goate, A. (2008). Using dimensional models of externalizing psychopathology to aid in gene identification. Archives of General Psychiatry, 65(3), 310-318.

Using dimensional models of externalizing psychopathology to aid in gene identification. / Dick, Danielle M.; Aliev, Fazil; Wang, Jen C.; Grucza, Richard A.; Schuckit, Marc; Kuperman, Samuel; Kramer, John; Hinrichs, Anthony; Bertelsen, Sarah; Budde, John P.; Hesselbrock, Victor; Porjesz, Bernice; Edenberg, Howard; Bierut, Laura Jean; Goate, Alison.

In: Archives of General Psychiatry, Vol. 65, No. 3, 03.2008, p. 310-318.

Research output: Contribution to journalArticle

Dick, DM, Aliev, F, Wang, JC, Grucza, RA, Schuckit, M, Kuperman, S, Kramer, J, Hinrichs, A, Bertelsen, S, Budde, JP, Hesselbrock, V, Porjesz, B, Edenberg, H, Bierut, LJ & Goate, A 2008, 'Using dimensional models of externalizing psychopathology to aid in gene identification', Archives of General Psychiatry, vol. 65, no. 3, pp. 310-318.
Dick DM, Aliev F, Wang JC, Grucza RA, Schuckit M, Kuperman S et al. Using dimensional models of externalizing psychopathology to aid in gene identification. Archives of General Psychiatry. 2008 Mar;65(3):310-318.
Dick, Danielle M. ; Aliev, Fazil ; Wang, Jen C. ; Grucza, Richard A. ; Schuckit, Marc ; Kuperman, Samuel ; Kramer, John ; Hinrichs, Anthony ; Bertelsen, Sarah ; Budde, John P. ; Hesselbrock, Victor ; Porjesz, Bernice ; Edenberg, Howard ; Bierut, Laura Jean ; Goate, Alison. / Using dimensional models of externalizing psychopathology to aid in gene identification. In: Archives of General Psychiatry. 2008 ; Vol. 65, No. 3. pp. 310-318.
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