Evidence map›Paper›PMID 41738161›Full record

ArticleAmerican journal of respiratory and critical care medicine2026

A trans-omics gene-smoking interaction study of lung cancer based on consortium data.

Ning Xie, Xiaowen Xu, Yanru Wang, Aoxuan Wang, Xiang Wang, Xuan Wang, Mengsheng Zhao, Jiacheng Zhou, Yongyue Wei, Manel Esteller and 9 more

Abstract read
In one paragraph

Article in American journal of respiratory and critical care medicine, 2026. 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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0citing papers 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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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

5 · Who and what money

Authors and funding

19 authors.

Ning XieDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Xiaowen XuDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Yanru WangDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Aoxuan WangDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Xiang WangDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Xuan WangDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Mengsheng ZhaoDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Jiacheng ZhouDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Yongyue WeiCenter for Public Health and Epidemic Preparedness and Response, Peking University, Beijing, China.ORCID 0000-0002-9378-8794
Manel EstellerCancer Epigenetics Group, Josep Carreras Leukaemia Research Institute, Barcelona, Catalonia, Spain.
Zhibin HuDepartment of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID 0000-0002-8277-5234
Hongbing ShenDepartment of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID 0000-0002-2581-5906
Rayjean J HungLunenfeld-Tanenbaum Research Institute, Sinai Health, University of Toronto, Toronto, Canada.
Christopher I AmosInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, United States.
Yi LiDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, United States.ORCID 0000-0003-1720-2760
David C ChristianiDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Feng ChenDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID 0000-0002-2699-7190
Yang ZhaoDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID 0000-0003-1393-7567
Ruyang ZhangDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID 0000-0003-3861-4297

Funding

Translational Research Support CoreP30ES000002 · NIEHS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI JAIME ELIZABETH HART · 1985 to 2026
$44.6M
The Boston Lung Cancer Survival CohortU01CA209414 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI David C Christiani · 2017 to 2026
$12.2M
Molecular and Genetic Analysis of Lung Cancer SurvivalR01CA092824 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI CHRISTIANI, DAVID C · 2002 to 2013
$5.9M
New Statistical Methods for Modelling Cancer OutcomesR01CA249096 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Yi Li · 2021 to 2026
$2.5M
National Natural Science Foundation of China 82220108002National Natural Science Foundation of China 82273737National Natural Science Foundation of China 82373690National Natural Science Foundation of China 82473728National Science and Technology Major Project 2024ZD0520000National Science and Technology Major Project 2024ZD0520003NCI NIH HHS R01 CA092824NCI NIH HHS R01 CA249096NCI NIH HHS U01 CA209414NIEHS NIH HHS P30 ES000002NIH HHS CA092824NIH HHS CA209414NIH HHS CA 249096NIH HHS CA249096NIH HHS ES000002Noncommunicable Chronic DiseasesOutstanding Young Teachers Training Program of Nanjing Medical UniversityPriority Academic Program Development of Jiangsu Higher Education Institutions
6 · The paper itself

Abstract

rationaleGenetically predicted molecular traits provide a cost-effective approach for identifying biomarkers and uncovering underlying biological mechanisms. We extended this framework to investigate gene-smoking interactions in lung cancer susceptibility.

objectivesTo identify trans-omics gene-smoking interactions affecting lung cancer risk and to assess how biomarkers modify effect of smoking.

methodsWe conducted the first trans-omics gene-smoking interaction study of lung cancer by integrating consortium-scale individual genotype data (27 737 cases vs 449 910 noncases) from the International Lung Cancer OncoArray Consortium (ILCCO-OncoArray), Transdisciplinary Research Into Cancer of the Lung (TRICL), Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the UK Biobank (UKB) with alliance-based summary-level molecular quantitative trait loci (xQTL) data, involving DNA methylation, gene expression, protein, and metabolite. Based on the identified biomarkers, we developed a molecular modifying score (MMS) to delineate gene-smoking interaction patterns and stratify smokers at high risk of lung cancer. MEASUREMENTS AND MAIN

resultsEight biomarkers showing significant interactions with smoking were identified through a 2-phase analytic strategy, comprising CpG sites in the nicotinic acetylcholine receptor region and gene RP11-326C3.14. The MMS, constructed by integrating these biomarkers with their effect estimates derived from meta-analysis of all available datasets, effectively stratified lung cancer risk among smokers. Trans-omics integrative analysis revealed functional relationships across molecular layers, particularly implicating the NELFE gene in smoking-related carcinogenesis pathways.

conclusionsThe trans-omics association study (xWAS) framework enables systematic discovery of trans-omics gene-environment interactions. The MMS effectively delineates the patterns of the interaction effects and facilitates risk stratification. Additionally, we launched a free online platform, LungCancer-xWAS-GxE (http://bigdata.njmu.edu.cn/LungCancer-xWAS-GxE/).

Indexed as

Gene-Environment InteractionLung NeoplasmsSmokingDNA MethylationFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedMultiomicsQuantitative Trait Locigene–smoking interactiongenome-wide association studylung cancertrans-omicsxWAS

Identifiers

PMID41738161
PMCPMC13365843

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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.