Evidence map›Paper›PMID 34313775›Full record

ArticleNicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco2021

Multiethnic Prediction of Nicotine Biomarkers and Association With Nicotine Dependence.

Andrew W Bergen, Christopher S McMahan, Stephen McGee, Carolyn M Ervin, Hilary A Tindle, Loïc Le Marchand, Sharon E Murphy, Daniel O Stram, Yesha M Patel, Sungshim L Park and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 31% of its field
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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Smoking drives an epigenetic memory of aberrant hematopoiesis.medRxiv : the preprint server for health sciences · 2026
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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

11 authors at 7 institutions in 1 country.

Andrew W BergenOregon Research Institute, Eugene, OR, USA.ORCID 0000-0002-1237-7644
Christopher S McMahanSchool of Mathematical and Statistical Sciences, Clemson University, Clemson, SC, USA.
Stephen McGeeBioRealm, LLC, Walnut, CA, USA.
Carolyn M ErvinBioRealm, LLC, Walnut, CA, USA.
Hilary A TindleDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Loïc Le MarchandCancer Epidemiology and University of Hawaii Cancer Center, University of Hawai'i, Honolulu, HI, USA.
Sharon E MurphyBiochemistry, Molecular Biology, and Biophysics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Daniel O StramDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Yesha M PatelDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Sungshim L ParkCancer Epidemiology and University of Hawaii Cancer Center, University of Hawai'i, Honolulu, HI, USA.
James W BaurleyBioRealm, LLC, Walnut, CA, USA.
BioRealm (United States) · USUniversity of Hawaiʻi at Mānoa · USUniversity of Southern California · USClemson University · USOregon Research Institute · USUniversity of Minnesota · USVA Tennessee Valley Healthcare System · US

Funding

University of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI Pallav Pokhrel · 1996 to 2026
$56.2M
Understanding Population Differences in Cancer: The MEC StudyU01CA164973 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI HAIMAN, CHRISTOPHER ALAN, LE MARCHAND, LOIC · 2015 to 2025
$37.4M
Untargeted Adductomics to Characterize Ethnic Differences in the Exposome of SmokersP01CA138338 · NCI · UNIVERSITY OF MINNESOTA · PI Daniel O Stram · 2010 to 2026
$33.4M
The Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2001 to 2012
$17.3M
RELAPSE: LINKING SCIENCE AND PRACTICEP50CA084724 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI FIORE, MICHAEL C · 1999 to 2003
$8.9M
Tobacco Dependence: Treatment and OutcomesP50DA019706 · NIDA · UNIVERSITY OF WISCONSIN-MADISON · PI FIORE, MICHAEL C · 2004 to 2008
$8.6M
Genome Wide Association Coordinating CenterU01HG004446 · NHGRI · UNIVERSITY OF WASHINGTON · PI WEIR, BRUCE S. · 2007 to 2011
$6.6M
Metabolism Informed Smoking Treatment in Medicaid and Medicare Patients: The MIST RCTR01CA232516 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI TINDLE, HILARY A. · 2019 to 2023
$3.6M
Smokescreen Translational (TL) Analysis PlatformR44AA027675 · NIAAA · BIOREALM · PI BAURLEY, JAMES WILLIAM, BERGEN, ANDREW W · 2018 to 2020
$1.7M
Smokescreen Translational (TL) Analysis PlatformR43DA041211 · NIDA · BIOREALM · PI BAURLEY, JAMES WILLIAM, BERGEN, ANDREW W · 2016 to 2016
$150k
NCI NIH HHS P01 CA089392NCI NIH HHS P01 CA138338NCI NIH HHS P30 CA071789NCI NIH HHS P50 CA084724NCI NIH HHS R01 CA232516NCI NIH HHS U01 CA164973NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004446NIAAA NIH HHS R44 AA027675NIDA NIH HHS P50 DA019706NIDA NIH HHS R43 DA041211
6 · The paper itself

Abstract

introductionThe nicotine metabolite ratio and nicotine equivalents are measures of metabolism rate and intake. Genome-wide prediction of these nicotine biomarkers in multiethnic samples will enable tobacco-related biomarker, behavioral, and exposure research in studies without measured biomarkers. AIMS AND

methodsWe screened genetic variants genome-wide using marginal scans and applied statistical learning algorithms on top-ranked genetic variants, age, ethnicity and sex, and, in additional modeling, cigarettes per day (CPD), (in additional modeling) to build prediction models for the urinary nicotine metabolite ratio (uNMR) and creatinine-standardized total nicotine equivalents (TNE) in 2239 current cigarette smokers in five ethnic groups. We predicted these nicotine biomarkers using model ensembles and evaluated external validity using dependence measures in 1864 treatment-seeking smokers in two ethnic groups.

resultsThe genomic regions with the most selected and included variants for measured biomarkers were chr19q13.2 (uNMR, without and with CPD) and chr15q25.1 and chr10q25.3 (TNE, without and with CPD). We observed ensemble correlations between measured and predicted biomarker values for the uNMR and TNE without (with CPD) of 0.67 (0.68) and 0.65 (0.72) in the training sample. We observed inconsistency in penalized regression models of TNE (with CPD) with fewer variants at chr15q25.1 selected and included. In treatment-seeking smokers, predicted uNMR (without CPD) was significantly associated with CPD and predicted TNE (without CPD) with CPD, time-to-first-cigarette, and Fagerström total score.

conclusionsNicotine metabolites, genome-wide data, and statistical learning approaches developed novel robust predictive models for urinary nicotine biomarkers in multiple ethnic groups. Predicted biomarker associations helped define genetically influenced components of nicotine dependence. IMPLICATIONS: We demonstrate development of robust models and multiethnic prediction of the uNMR and TNE using statistical and machine learning approaches. Variants included in trained models for nicotine biomarkers include top-ranked variants in multiethnic genome-wide studies of smoking behavior, nicotine metabolites, and related disease. Association of the two predicted nicotine biomarkers with Fagerström Test for Nicotine Dependence items supports models of nicotine biomarkers as predictors of physical dependence and nicotine exposure. Predicted nicotine biomarkers may facilitate tobacco-related disease and treatment research in samples with genomic data and limited nicotine metabolite or tobacco exposure data.

Indexed as

Tobacco ProductsTobacco Use DisorderBiomarkersHumansNicotineSmokingBiomarkersNicotine

Identifiers

PMID34313775
PMCPMC8757310
OpenAlexW3186455575

What OpenQuestion holds

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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.