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Cross-generational transcriptomic effects of alcohol use disorder in third generation offspring
Shirley Y Hill1,2,3, Gregg E Homanics4,5,6, Sean Farris4,5,7
1Department of Psychiatry, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, 3811 O' Hara St., Pittsburgh, PA, 15213, USA. syh50@pitt.edu.
Scientific Reports
|May 20, 2026
Summary
Generational alcohol misuse impacts offspring gene expression. Parental or grandparental alcohol use disorder (AUD) was linked to significant gene expression differences in adolescents, potentially increasing disease risk.
Area of Science:
- Genetics
- Molecular Biology
- Public Health
Background:
- Alcohol use disorder (AUD) is a prevalent global health issue with known generational transmission.
- While the health effects of alcohol misuse are established, the impact of ancestral alcohol misuse on offspring gene expression and disease burden remains largely unknown.
Purpose of the Study:
- To investigate the association between familial alcohol use disorder (AUD) and gene expression in offspring.
- To determine if parental or grandparental AUD influences offspring gene expression, potentially contributing to future disease risk.
Main Methods:
- A study contrasting individuals with and without a family history of AUD (parental or grandparental).
- Gene expression analysis in adolescent blood samples, collected before significant substance use.
- Maternal interviews regarding prenatal alcohol and substance use.
Main Results:
- Significant differences in gene expression were observed between offspring of parents/grandparents with AUD and controls.
- Preconception high-level alcohol use by parents/grandparents is associated with altered offspring blood gene expression.
- Pathway enrichment analysis indicated overrepresentation in immune system and cancer development pathways.
Conclusions:
- Familial alcohol use disorder is associated with significant, heritable changes in offspring gene expression.
- These gene expression alterations may predispose offspring to immune system dysfunction and increased cancer risk.
- Further research is warranted to elucidate the mechanisms and long-term health consequences.
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