Partitioning the Genomic Components of Behavioral Disinhibition and Substance Use (Disorder) Using Genomic Structural...

Area of Science:

• Behavioral genetics
• Psychiatric genetics
• Quantitative genetics

Background:

• Externalizing behaviors, including risk-taking and impulsivity, are complex traits.
• Substance use (SUB), substance use disorder (SUD), and behavioral disinhibition (BD) are key facets of externalizing behaviors.
• Previous research suggests shared genetic underpinnings for these traits.

Purpose of the Study:

• To investigate the genetic covariance partitioning among SUB, SUD, and BD traits.
• To determine the extent to which genetic variation in BD is independent of SUB and SUD.

Main Methods:

• Utilized European ancestry genome-wide association study (GWAS) statistics for SUB, SUD, and BD traits.
• Constructed single-factor measurement models for each trait.
• Applied correlated factors models and Cholesky decomposition to assess genetic covariance.

Main Results:

• High genetic correlations were observed between SUD and SUB (r_g = 0.803), BD and SUD (r_g = 0.774), and BD and SUB (r_g = 0.778).
• In initial models, 33% of BD variance remained after accounting for SUD and SUB.
• The majority of genetic covariance was shared, with a small fraction of BD variation acting independently of SUB and SUD.

Conclusions:

• Genetic architecture of externalizing behaviors shows substantial overlap between SUB, SUD, and BD.
• A significant portion of behavioral disinhibition's genetic basis is shared with substance use and substance use disorder.
• Further research is needed to explore the specific genetic and molecular correlates of BD-specific variation.