Longitudinal effects and environmental moderation of ALDH2 and ADH1B gene variants on substance use from age 14 to 40

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Alcohol use and dependence are strongly affected by variation in aldehyde dehydrogenase (ALDH2) and, to a lesser extent, alcohol dehydrogenase (ADH1B) genes. We use this genetic variation with an adoption design to test the causal role of alcohol use on other drug use, as well as the moderating role of adoptive parent, sibling, and peer alcohol use. Longitudinal models were run on 412 genotyped adopted individuals of East Asian ancestry with multiple assessments between ages 14 and 40. We found robust associations between alcohol frequency, quantity, and maximum drinks and ALDH2, but not ADH1B, status. The magnitude of the ALDH2 protective effect increased with age, particularly for maximum drinks, though estimates were smaller than previously reported in ancestrally similar individuals in East/North-East Asian countries. These results suggest that sociocultural factors in Minnesota may reduce the protective effects of ALDH2. We found that peer alcohol use, but not parent or sibling use, predicted adopted offspring's use, and that these environmental influences did not vary by ALDH2 status. Finally, we did not find strong evidence of associations between ALDH2 status and tobacco, marijuana, or illegal drug use, contrary to expectation if alcohol serves as a gateway to use of other drugs.

Original languageEnglish (US)
Pages (from-to)1856-1864
Number of pages9
JournalDevelopment and psychopathology
Issue number5
StatePublished - Dec 14 2022

Bibliographical note

Funding Information:
This work was supported by NIH grants AA11886, MH066140, AA009367, DA024417, R01DA044283, R01DA042755, and T32DA050560.

Publisher Copyright:


  • Keywords: Alcohol
  • Mendelian randomization
  • development
  • longitudinal
  • trajectory


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