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.
Bibliographical noteFunding Information:
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.
- Adoption studies
- Antisocial behavior
- Gene association
- Substance use disorders
- Twin studies