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Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.

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Title: Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.
Authors: Schaefer, Jonathan D., Jang, Seon-Kyeong, Clark, D. Angus, Deak, Joseph D., Hicks, Brian M., Iacono, William G., Liu, Mengzhen, McGue, Matt, Vrieze, Scott I., Wilson, Sylia
Source: Psychological Medicine. Apr2023, Vol. 53 Issue 6, p2296-2306. 11p.
Subjects: Substance abuse risk factors, Structural equation modeling, Genetics, Cannabis (Genus), Nicotine, Risk assessment, Genome-wide association studies, Alcohol drinking, Research funding, Prediction models, Adults, Adolescence
Abstract: Background: Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset. Methods: PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models. Results: Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence. Conclusions: PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use. [ABSTRACT FROM AUTHOR]
Copyright of Psychological Medicine is the property of Cambridge University Press 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.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.
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  Data: <searchLink fieldCode="AR" term="%22Schaefer%2C+Jonathan+D%2E%22">Schaefer, Jonathan D.</searchLink><br /><searchLink fieldCode="AR" term="%22Jang%2C+Seon-Kyeong%22">Jang, Seon-Kyeong</searchLink><br /><searchLink fieldCode="AR" term="%22Clark%2C+D%2E+Angus%22">Clark, D. Angus</searchLink><br /><searchLink fieldCode="AR" term="%22Deak%2C+Joseph+D%2E%22">Deak, Joseph D.</searchLink><br /><searchLink fieldCode="AR" term="%22Hicks%2C+Brian+M%2E%22">Hicks, Brian M.</searchLink><br /><searchLink fieldCode="AR" term="%22Iacono%2C+William+G%2E%22">Iacono, William G.</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Mengzhen%22">Liu, Mengzhen</searchLink><br /><searchLink fieldCode="AR" term="%22McGue%2C+Matt%22">McGue, Matt</searchLink><br /><searchLink fieldCode="AR" term="%22Vrieze%2C+Scott+I%2E%22">Vrieze, Scott I.</searchLink><br /><searchLink fieldCode="AR" term="%22Wilson%2C+Sylia%22">Wilson, Sylia</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Psychological+Medicine%22">Psychological Medicine</searchLink>. Apr2023, Vol. 53 Issue 6, p2296-2306. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Substance+abuse+risk+factors%22">Substance abuse risk factors</searchLink><br /><searchLink fieldCode="DE" term="%22Structural+equation+modeling%22">Structural equation modeling</searchLink><br /><searchLink fieldCode="DE" term="%22Genetics%22">Genetics</searchLink><br /><searchLink fieldCode="DE" term="%22Cannabis+%28Genus%29%22">Cannabis (Genus)</searchLink><br /><searchLink fieldCode="DE" term="%22Nicotine%22">Nicotine</searchLink><br /><searchLink fieldCode="DE" term="%22Risk+assessment%22">Risk assessment</searchLink><br /><searchLink fieldCode="DE" term="%22Genome-wide+association+studies%22">Genome-wide association studies</searchLink><br /><searchLink fieldCode="DE" term="%22Alcohol+drinking%22">Alcohol drinking</searchLink><br /><searchLink fieldCode="DE" term="%22Research+funding%22">Research funding</searchLink><br /><searchLink fieldCode="DE" term="%22Prediction+models%22">Prediction models</searchLink><br /><searchLink fieldCode="DE" term="%22Adults%22">Adults</searchLink><br /><searchLink fieldCode="DE" term="%22Adolescence%22">Adolescence</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset. Methods: PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models. Results: Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence. Conclusions: PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Psychological Medicine is the property of Cambridge University Press 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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        Value: 10.1017/S0033291721004116
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      – Code: eng
        Text: English
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        PageCount: 11
        StartPage: 2296
    Subjects:
      – SubjectFull: Substance abuse risk factors
        Type: general
      – SubjectFull: Structural equation modeling
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      – SubjectFull: Genetics
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      – SubjectFull: Cannabis (Genus)
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      – SubjectFull: Nicotine
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      – SubjectFull: Risk assessment
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      – SubjectFull: Genome-wide association studies
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      – SubjectFull: Alcohol drinking
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      – TitleFull: Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.
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              Text: Apr2023
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