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Psychometric and Genetic Architecture of Substance Use Disorder and Behavioral Disinhibition Measures for Gene Association Studies

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Abstract

Using large twin, family, and adoption studies conducted at the Minnesota Center for Twin and Family Research, we describe our efforts to develop measures of substance use disorder (SUD) related phenotypes for targets in genome wide association analyses. Beginning with a diverse set of relatively narrow facet-level measures, we identified 5 constructs of intermediate complexity: nicotine, alcohol consumption, alcohol dependence, illicit drug, and behavioral disinhibition. The 5 constructs were moderately correlated (mean r = .57) reflecting a general externalizing liability to substance abuse and antisocial behavior. Analyses of the twin and adoption data revealed that this general externalizing liability accounted for much of the genetic risk in each of the intermediate-level constructs, though each also exhibited significant unique genetic and environmental risk. Additional analyses revealed substantial effects for age and sex, significant shared environmental effects, and that the mechanism of these shared environmental effects operates via siblings rather than parents. Our results provide a foundation for genome wide association analyses to detect risk alleles for SUDs as well as novel insights into genetic and environmental risk for SUDs.

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Notes

  1. The analysis reported in the text differs slightly from the figure depicting mean behavioral disinhibition scores as a function of age. Specifically, the analysis discussed in the text fits a linear regression model to the full sample and detects overall negative effects for both age and age2. In contrast, for the purpose of better visual presentation, the figure depicts fitting separate linear regression models for offspring (showing a linear increase) and parent (showing a linear decrease) participants.

  2. To ensure the biometric analyses would not be affected by any potential group differences in mean levels of externalizing behaviors, we tested for group differences between offspring from the MTFS and SIBS samples on the lower-order factors and higher-order externalizing factor. Offspring from the MTFS and SIBS exhibited comparable scores with the mean Cohen’s d = −.03 (range −.13 to .09).

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Acknowledgments

This work was supported in part by USPS grants U01 DA024417, R01 DA005147, R01 DA013240, R01 AA009367, R01 AA011886, and R01 MH066140. Brian M. Hicks was supported by K01 DA025868. Stephen M. Malone was supported by K01 AA015621.

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Authors and Affiliations

  1. Department of Psychiatry, University of Michigan, 4250 Plymouth Rd, Ann Arbor, MI, 48105, USA

    Brian M. Hicks

  2. Department of Psychology, Northwestern University, Evanston, IL, USA

    Benjamin D. Schalet

  3. Department of Psychology, University of Minnesota, Minneapolis, MN, USA

    Stephen M. Malone, William G. Iacono & Matt McGue

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  1. Brian M. Hicks
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  2. Benjamin D. Schalet
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  3. Stephen M. Malone
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  4. William G. Iacono
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Correspondence to Brian M. Hicks.

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Hicks, B.M., Schalet, B.D., Malone, S.M. et al. Psychometric and Genetic Architecture of Substance Use Disorder and Behavioral Disinhibition Measures for Gene Association Studies. Behav Genet 41, 459–475 (2011). https://doi.org/10.1007/s10519-010-9417-2

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