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

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Title: Partitioning the Genomic Components of Behavioral Disinhibition and Substance Use (Disorder) Using Genomic Structural Equation Modeling.
Authors: Horwitz, Tanya B. (AUTHOR), Zorina-Lichtenwalter, Katerina (AUTHOR), Gustavson, Daniel E. (AUTHOR), Grotzinger, Andrew D. (AUTHOR), Stallings, Michael C. (AUTHOR)
Source: Behavior Genetics. Sep2024, Vol. 54 Issue 5, p386-397. 12p.
Subjects: Genome-wide association studies, Behavior genetics, Structural equation modeling, Substance abuse, Externalizing behavior
Abstract: Externalizing behaviors encompass manifestations of risk-taking, self-regulation, aggression, sensation-/reward-seeking, and impulsivity. Externalizing research often includes substance use (SUB), substance use disorder (SUD), and other (non-SUB/SUD) "behavioral disinhibition" (BD) traits. Genome-wide and twin research have pointed to overlapping genetic architecture within and across SUB, SUD, and BD. We created single-factor measurement models—each describing SUB, SUD, or BD traits—based on mutually exclusive sets of European ancestry genome-wide association study (GWAS) statistics exploring externalizing variables. We then assessed the partitioning of genetic covariance among the three facets using correlated factors models and Cholesky decomposition. Even when the residuals for indicators relating to the same substance were correlated across the SUB and SUD factors, the two factors yielded a large correlation (rg = 0.803). BD correlated strongly with the SUD (rg = 0.774) and SUB (rg = 0.778) factors. In our initial decompositions, 33% of total BD variance remained after partialing out SUD and SUB. The majority of covariance between BD and SUB and between BD and SUD was shared across all factors, and, within these models, only a small fraction of the total variation in BD operated via an independent pathway with SUD or SUB outside of the other factor. When only nicotine/tobacco, cannabis, and alcohol were included for the SUB/SUD factors, their correlation increased to rg = 0.861; in corresponding decompositions, BD-specific variance decreased to 27%. Further research can better elucidate the properties of BD-specific variation by exploring its genetic/molecular correlates. [ABSTRACT FROM AUTHOR]
Copyright of Behavior Genetics is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Externalizing behaviors encompass manifestations of risk-taking, self-regulation, aggression, sensation-/reward-seeking, and impulsivity. Externalizing research often includes substance use (SUB), substance use disorder (SUD), and other (non-SUB/SUD) "behavioral disinhibition" (BD) traits. Genome-wide and twin research have pointed to overlapping genetic architecture within and across SUB, SUD, and BD. We created single-factor measurement models—each describing SUB, SUD, or BD traits—based on mutually exclusive sets of European ancestry genome-wide association study (GWAS) statistics exploring externalizing variables. We then assessed the partitioning of genetic covariance among the three facets using correlated factors models and Cholesky decomposition. Even when the residuals for indicators relating to the same substance were correlated across the SUB and SUD factors, the two factors yielded a large correlation (rg = 0.803). BD correlated strongly with the SUD (rg = 0.774) and SUB (rg = 0.778) factors. In our initial decompositions, 33% of total BD variance remained after partialing out SUD and SUB. The majority of covariance between BD and SUB and between BD and SUD was shared across all factors, and, within these models, only a small fraction of the total variation in BD operated via an independent pathway with SUD or SUB outside of the other factor. When only nicotine/tobacco, cannabis, and alcohol were included for the SUB/SUD factors, their correlation increased to rg = 0.861; in corresponding decompositions, BD-specific variance decreased to 27%. Further research can better elucidate the properties of BD-specific variation by exploring its genetic/molecular correlates. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Behavior Genetics is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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