ArticleMolecular psychiatry2022
Chromatin architecture in addiction circuitry identifies risk genes and potential biological mechanisms underlying cigarette smoking and alcohol use traits.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Gene expression differences associated with alcohol use disorder in human brain.Molecular psychiatry · 2025Pooled it
- Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.Nature human behaviour · 2024Pooled it
- The resting-state brain activity signatures for addictive disorders.Med (New York, N.Y.) · 2024Pooled it
- Extensive genetic interactions (epistasis) linked to alcohol use disorder in a high-risk population.Communications biology · 2026Article
- AT1R in Central Nervous System Disorders: Unveiling Novel Mechanisms and Therapeutic Avenues for Addiction.Addiction biology · 2026Review
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Shared and unique 3D genomic features of substance use disorders across multiple cell types.medRxiv : the preprint server for health sciences · 2025Article
- Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder.Translational psychiatry · 2025Article
- Just a SNP away: The future ofCell insight · 2025Review
- Systematic dissection of pleiotropic loci and critical regulons in excitatory neurons and microglia relevant to neuropsychiatric and ocular diseases.Translational psychiatry · 2025Article
- A multi-ancestry cerebral cortex transcriptome-wide association study identifies genes associated with smoking behaviors.Molecular psychiatry · 2024Article
- Review
- Neuroscience in addiction research.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Neurogenetic and multi-omic sources of overlap among sensation seeking, alcohol consumption, and alcohol use disorder.Addiction biology · 2024Article
- Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes.medRxiv : the preprint server for health sciences · 2023Article
- Chromatin loop dynamics during cellular differentiation are associated with changes to both anchor and internal regulatory features.Genome research · 2023Article
- Neurogenetic and multi-omic sources of overlap among sensation seeking, alcohol consumption, and alcohol use disorder.medRxiv : the preprint server for health sciences · 2023Article
- Article
- The Genetically Informed Neurobiology of Addiction (GINA) model.Nature reviews. Neuroscience · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Cigarette smoking and alcohol use are among the most prevalent substances used worldwide and account for a substantial proportion of preventable morbidity and mortality, underscoring the public health significance of understanding their etiology. Genome-wide association studies (GWAS) have successfully identified genetic variants associated with cigarette smoking and alcohol use traits. However, the vast majority of risk variants reside in non-coding regions of the genome, and their target genes and neurobiological mechanisms are unknown. Chromosomal conformation mappings can address this knowledge gap by charting the interaction profiles of risk-associated regulatory variants with target genes. To investigate the functional impact of common variants associated with cigarette smoking and alcohol use traits, we applied Hi-C coupled MAGMA (H-MAGMA) built upon cortical and newly generated midbrain dopaminergic neuronal Hi-C datasets to GWAS summary statistics of nicotine dependence, cigarettes per day, problematic alcohol use, and drinks per week. The identified risk genes mapped to key pathways associated with cigarette smoking and alcohol use traits, including drug metabolic processes and neuronal apoptosis. Risk genes were highly expressed in cortical glutamatergic, midbrain dopaminergic, GABAergic, and serotonergic neurons, suggesting them as relevant cell types in understanding the mechanisms by which genetic risk factors influence cigarette smoking and alcohol use. Lastly, we identified pleiotropic genes between cigarette smoking and alcohol use traits under the assumption that they may reveal substance-agnostic, shared neurobiological mechanisms of addiction. The number of pleiotropic genes was ~26-fold higher in dopaminergic neurons than in cortical neurons, emphasizing the critical role of ascending dopaminergic pathways in mediating general addiction phenotypes. Collectively, brain region- and neuronal subtype-specific 3D genome architecture helps refine neurobiological hypotheses for smoking, alcohol, and general addiction phenotypes by linking genetic risk factors to their target genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.