Evidence map›Paper›PMID 40449208›Full record

ArticleDrug and alcohol dependence2025

Polygenic risk and childhood adversity as moderators of drug and alcohol withdrawal symptoms.

Angela Han, Christal N Davis, Zeal Jinwala, Jackson SooHoo, Joel Gelernter, Richard Feinn, Henry R Kranzler

Abstract read
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In one paragraph

Article in Drug and alcohol dependence, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from 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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

7 authors.

Angela HanCenter for Studies of Addiction, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Christal N DavisCenter for Studies of Addiction, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Mental Illness Research, Education, and Clinical Center, Crescenz VAMC, Philadelphia, PA 19104, USA.
Zeal JinwalaCenter for Studies of Addiction, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Mental Illness Research, Education, and Clinical Center, Crescenz VAMC, Philadelphia, PA 19104, USA.
Jackson SooHooCenter for Studies of Addiction, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Joel GelernterDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; VA Connecticut Healthcare System, West Haven, CT 06516, USA.
Richard FeinnDepartment of Medical Sciences, Frank H. Netter School of Medicine at Quinnipiac University, North Haven, CT 06473, USA.
Henry R KranzlerCenter for Studies of Addiction, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Mental Illness Research, Education, and Clinical Center, Crescenz VAMC, Philadelphia, PA 19104, USA. Electronic address: kranzler@pennmedicine.upenn.edu.

Funding

Leveraging GWAS Findings to Map Variants and Identify Novel Effector Genes for Alcohol-Related TraitsR01AA030056 · NIAAA · UNIVERSITY OF PENNSYLVANIA · PI Struan F A Grant, MATTHEW S KAYSER · 2023 to 2026
$2.5M
NIAAA NIH HHS R01 AA030056
6 · The paper itself

Abstract

introductionReducing or stopping substance use can result in withdrawal symptoms in physically dependent individuals. Appropriate management of withdrawal symptoms may be critical to the safety of individuals with substance use disorders (SUDs) and could help prevent a return to substance use. Although childhood adversity and genetic factors contribute to the development of SUDs, their individual and joint effects on withdrawal symptoms and severity are less clear. This study is a secondary analysis of existing data in which we examined the main and interactive effects of genetic variation and adverse childhood events (ACEs) on the severity of withdrawal from tobacco, alcohol, and opioids.

methodsParticipants were 10,275 individuals (4851 of African-like (AFR) ancestry and 5424 of European-like (EUR) ancestry) from the Yale-Penn sample. Tobacco, alcohol, and opioid withdrawal symptoms and 10 ACEs were measured using a semi-structured diagnostic instrument. Multivariate regression models examined the association of SUD polygenic scores (PGS), ACEs, and their interaction with withdrawal severity and individual withdrawal symptoms.

resultsACEs were positively associated with withdrawal severity, except for opioid withdrawal among AFR individuals. Among EUR individuals, PGS were positively associated with tobacco and alcohol withdrawal severity. There was a negative interaction between ACEs and PGS on tobacco withdrawal severity and specific tobacco withdrawal symptoms.

conclusionsIndividuals who experience ACEs and, to a lesser extent, those with higher PGS for SUDs, are susceptible to more severe withdrawal symptoms. In EUR individuals, there was evidence for a complex interplay of genetic and environmental factors on substance withdrawal. These exploratory findings require independent validation.

Indexed as

Adverse Childhood ExperiencesMultifactorial InheritanceSubstance-Related DisordersSubstance Withdrawal SyndromeAdultAlcoholismBlack PeopleFemaleHumansMaleMiddle AgedRisk FactorsWhite PeopleYoung Adult

Identifiers

PMID40449208
PMCPMC13050494

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LicenceCC BY-NC-ND
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Registered trials

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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.