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Indirect Genetic Effects on Alcohol Use Disorder and Nicotine Dependence.

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Summary

Intergenerational transmission of alcohol use disorder (AUD) and nicotine dependence (ND) risk is mainly due to direct genetic effects. Indirect genetic effects, influenced by the family environment, play a minor role, primarily in smoking quantity.

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Area of Science:

  • Behavioral Genetics
  • Psychiatric Genetics
  • Substance Use Disorders

Background:

  • Substance use disorders (SUDs) exhibit familial aggregation, but the mechanisms of intergenerational transmission are not fully understood.
  • Investigating indirect genetic effects, where parental genotypes influence offspring phenotypes through the family environment, is crucial for understanding transmission.

Purpose of the Study:

  • To investigate indirect genetic effects on alcohol use disorder (AUD) and nicotine dependence (ND).
  • To identify family environmental factors mediating these indirect genetic effects.

Main Methods:

  • Utilized transmitted and non-transmitted polygenic scores (PGS) for problematic alcohol use, tobacco use disorder, and general addiction liability.
  • Analyzed data from 5972 European-ancestry adult offspring and genotyped parents (Lifelines cohort, Netherlands).
  • Meta-analyzed AUD findings with the Brisbane Longitudinal Twin Study (N=1368, Australia) and employed structural equation modeling.

Main Results:

  • Transmitted PGS strongly predicted AUD and ND outcomes, including AUD diagnosis (OR=1.20).
  • Non-transmitted PGS, reflecting indirect genetic effects, were negligible for clinical syndrome outcomes.
  • A significant indirect genetic effect was observed for cigarettes per day, mediated by parental smoking but not socioeconomic status.

Conclusions:

  • Intergenerational transmission of AUD and ND risk is primarily driven by direct genetic effects.
  • Indirect genetic effects contribute modestly, particularly to smoking quantity, via parental behavior.
  • Further research with larger samples and cross-trait analyses is needed to fully elucidate transmission mechanisms.