ArticleAlcoholism, clinical and experimental research2021
Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use.
Article in Alcoholism, clinical and experimental research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Independent Heritability of Aversive Learning Influences on Cocaine-Seeking and Punishment Resistance in Rats.eNeuro · 2026Article
- Bulk and single-cell transcriptomic brain data identify overlapping processes and cell-types with human AUD and mammalian models of alcohol use.Translational psychiatry · 2026Article
- Testing associations between human anxiety and genes previously implicated by mouse anxiety models.Genes, brain, and behavior · 2023Article
- Multi-omics cannot replace sample size in genome-wide association studies.Genes, brain, and behavior · 2023Article
- Gene expression genetics of the striatum of Diversity Outbred mice.Scientific data · 2023Article
- Polygenic influences on the behavioral effects of alcohol withdrawal in a mixed-ancestry population from the collaborative study on the genetics of alcoholism (COGA).Molecular and cellular neurosciences · 2023Article
- Gene expression genetics of the striatum of Diversity Outbred mice.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundRodent paradigms and human genome-wide association studies (GWAS) on drug use have the potential to provide biological insight into the pathophysiology of addiction.
methodsUsing GeneWeaver, we created rodent alcohol and nicotine gene-sets derived from 19 gene expression studies on alcohol and nicotine outcomes. We partitioned the SNP heritability of these gene-sets using four large human GWAS: (1) alcoholic drinks per week, (2) problematic alcohol use, (3) cigarettes per day, and (4) smoking cessation. We benchmarked our findings with curated human alcohol and nicotine addiction gene-sets and performed specificity analyses using other rodent gene-sets (e.g., locomotor behavior) and other human GWAS (e.g., height).
resultsThe rodent alcohol gene-set was enriched for heritability of drinks per week, cigarettes per day, and smoking cessation, but not problematic alcohol use. However, the rodent nicotine gene-set was not significantly associated with any of these traits. Both rodent gene-sets showed enrichment for several non-substance-use GWAS, and the extent of this relationship tended to increase as a function of trait heritability. In general, larger gene-sets demonstrated more significant enrichment. Finally, when evaluating human traits with similar heritabilities, both rodent gene-sets showed greater enrichment for substance use traits.
conclusionOur results suggest that rodent gene expression studies can help to identify genes that contribute to the heritability of some substance use traits in humans, yet there was less specificity than expected. We outline various limitations, interpretations, and considerations for future research.
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