Evidence map›Paper›PMID 40174410›Full record

Trial reportPsychiatry research2025

Sex dependent genetic architecture of biochemically verified tobacco use.

Meghan J Chenoweth, Caryn Lerman, Jo Knight, Rachel F Tyndale

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Psychiatry research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01314001 (Pharmacogenetics of Nicotine Addiction Treatment), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

NCT01314001 phase3completednot on this map

Pharmacogenetics of Nicotine Addiction Treatment (PNAT)

TypeinterventionalSponsorUniversity of PennsylvaniaRan2010 to 2014Enrolled1,246ConditionsNicotine AddictionArmsVarenicline, Placebo, Transdermal Nicotine
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

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

4 authors.

Meghan J ChenowethCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: meghan.chenoweth@utoronto.ca.
Caryn LermanUSC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: Caryn.Lerman@med.usc.edu.
Jo KnightDepartment of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Data Science Institute and Lancaster University Medical School, Lancaster, UK. Electronic address: jo.knight@lancaster.uk.
Rachel F TyndaleCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: r.tyndale@utoronto.ca.

Funding

University of Toronto Coordinating Genetics Core & Clinical Trial SiteU01DA020830 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI TYNDALE, RACHEL FYNVOLA · 2005 to 2014
$22.4M
Helping African American Light Smokers QuitR01CA091912 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI COX, LISA SANDERSON · 2001 to 2010
$5.6M
Concurrent substance use and psychiatric disorders: a pipeline to investigate shared genomic liability and causal effectsR21DA057542 · NIDA · CENTRE FOR ADDICTION AND MENTAL HEALTH · PI CHENOWETH, MEGHAN · 2023 to 2024
$288k
NCI NIH HHS R01 CA091912NIDA NIH HHS R21 DA057542NIDA NIH HHS U01 DA020830
6 · The paper itself

Abstract

backgroundTobacco use differs by genetics and sex, and dose-dependently increases the risk for numerous diseases. Nicotine is metabolized to cotinine (COT) which is further metabolized to 3'hydroxycotinine (3HC). COT and COT+3HC are biomarkers which capture tobacco intake more accurately than self-reported measures such as cigarettes/day. It is currently not known whether genetic risk factors for heavier tobacco intake, measured using these biomarkers, differ by sex.

methodsWe conducted a genome-wide genotype-by-sex (GxS) interaction analysis of COT and COT+3HC measured from blood in European treatment-seeking smokers (n = 541 males, n = 389 females) (NCT01314001). Linear regression models included Genotypes (coded additively), Sex, a GxS interaction term, covariates, and all covariate-by-genotype and covariate-by-sex interaction terms.

resultsFor COT, five suggestive (P < 5 × 10

conclusionsOur findings suggest that the genetic architecture of tobacco intake, measured accurately using biomarkers, differs between women and men. A more granular understanding of factors influencing tobacco intake in women versus men may identify risk factors for heavier use and sex-specific opportunities to promote smoking cessation and mitigate disease risk. IMPLICATIONS: This genome-wide interaction study suggested that some of the genetic influences on tobacco intake, measured accurately using biomarkers, differ by sex. The loci identified in our study could be a starting point for developing new genetic biomarkers that predict sex-specific differences in tobacco intake and disease risk.

Indexed as

CotinineSex CharacteristicsTobacco UseAdultBiomarkersFemaleGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideBiomarkersCotininehydroxycotinine3′hydroxycotinineBiomarkersCotinineGenome-wide interaction studySex differencesTobacco dependence

Identifiers

PMID40174410
PMCPMC13196733

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.