Evidence map›Paper›PMID 40322892›Full record

ArticleAlcohol, clinical & experimental research2025

Multi-ancestry genome-wide association study of topiramate's effects on heavy alcohol use.

Christal N Davis, Zeal Jinwala, Amy C Justice, Christopher T Rentsch, Henry R Kranzler

Abstract read
In one paragraph

Article in Alcohol, clinical & experimental research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Christal N DavisMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.ORCID 0000-0003-3974-5598
Zeal JinwalaMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
Amy C JusticeVeterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA.ORCID 0000-0003-0139-5502
Christopher T RentschDepartment of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
Henry R KranzlerMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-1018-0450

Funding

BLRD VA I01 BX003341VISN 4 Mental Illness Research, Education, and Clinical Center
6 · The paper itself

Abstract

backgroundTopiramate reduces alcohol consumption in individuals who drink heavily. Candidate gene studies aimed at identifying genetic variants that predict topiramate's effects on drinking have yielded inconsistent findings. To identify genetic variation associated with treatment response, we conducted a genome-wide association study (GWAS) among participants in the Million Veteran Program (MVP) who initiated topiramate treatment.

methodsUsing electronic health records, we identified individuals who were dispensed topiramate for at least 60 days for any indication (i.e., the index event). Alcohol consumption was assessed using Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores during the year prior to topiramate exposure (pre index) and at least 60 days after initiating topiramate but within 6 months of drug discontinuation (post index). The final GWAS sample included 8386 individuals who reported alcohol consumption (i.e., AUDIT-C score > 0) during the preceding year. We calculated polygenic scores (PGS) for topiramate treatment response in the Yale-Penn sample (n = 10,275) and examined associations with 692 phenotypes using a phenome-wide association study.

resultsIn the cross-ancestry GWAS meta-analysis, 35 loci had suggestive associations, though none reached genome-wide significance. Topiramate response PGS had nominally significant associations with lower rates of alcohol-related liver disease, older age at alcohol use disorder diagnosis, and higher frequency of alcohol use.

conclusionsAlthough no loci reached genome-wide significance, the suggestive variants identified in the cross-ancestry meta-analysis are promising candidates for future investigation. Larger studies are needed to identify significant genetic predictors of topiramate response and advance precision medicine strategies for treating AUD.

Indexed as

Alcohol DrinkingAlcoholismGenome-Wide Association StudyTopiramateAdultAgedFemaleHumansMaleMiddle AgedTopiramatealcohol use disordergenome‐wide association studyprecision medicinetopiramatetreatment response

Identifiers

PMID40322892
PMCPMC12174493

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.