Evidence map›Paper›PMID 42414885›Full record

ArticleGenes & nutrition2026

Polyunsaturated fatty acids modulation of smoking-related epigenetics and pulmonary outcomes.

Bonnie K Patchen, Woei-Yuh Saw, E Kate Phillips, Bruce D Levy, Aldric Rosario, Michael H Cho, Edwin K Silverman, Dana B Hancock, Patricia A Cassano, Dawn L DeMeo

Abstract read
In one paragraph

Article in Genes & nutrition, 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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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

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

10 authors.

Bonnie K PatchenChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, USA.
Woei-Yuh SawChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, USA.
E Kate PhillipsChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, USA.
Bruce D LevyHarvard Medical School, Boston, USA.
Aldric RosarioChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, USA.
Michael H ChoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, USA.
Edwin K SilvermanChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, USA.
Dana B HancockRTI International, Durham, USA.
Patricia A CassanoDivision of Nutritional Sciences, Cornell University, Ithaca, USA.
Dawn L DeMeoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, USA. redld@channing.harvard.edu.

Funding

SYSTEMS APPROACHES TO THE EPIDEMIOLOGY, GENETICS AND GENOMICS OF LUNG DISEASEST32HL007427 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI DAWN L DEMEO, Edwin K Silverman · 1985 to 2026
$13.6M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
Nutritional Omics of Pulmonary Function DeclineR01HL149352 · NHLBI · RESEARCH TRIANGLE INSTITUTE · PI CASSANO, PATRICIA A, HANCOCK, DANA B · 2019 to 2022
$3.1M
NHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL149352NHLBI NIH HHS T32 HL007427NHLBI NIH HHS U01 HL120393NIEHS NIH HHS HHSN268201600032CNIH HHS T32 HL007427
6 · The paper itself

Abstract

backgroundCigarette smoking results in epigenetic alterations that persist after smoking cessation and is a major risk factor for chronic lung disease. Polyunsaturated fatty acids (PUFAs) may promote epigenetic recovery and support lung health. We aimed to characterize PUFA biomarker associations with lung phenotypes in high-risk populations with a smoking history and determine whether smoking-related DNA methylation (DNAm) mediates these associations.

methodsIn this observational study we analyzed blood-based omega-3 and omega-6 PUFA biomarkers, spirometry, chest computed tomography (CT) measures, and smoking-related DNAm in 3857 former and current smokers in the Genetic Epidemiology of COPD (COPDGene) study. PUFA associations with lung phenotypes and DNAm were modeled with robust linear regression and linear mixed models. Mediation analysis estimated PUFA effects mediated through DNAm. Models adjusted for demographics, smoking history, genotype principal components, and, where relevant, cell type proportions and CT scanner. Replication in blood and extension to lung tissue were tested in the Lung Tissue Resource Consortium (LTRC).

resultsHigher omega-3s were associated with higher lung function, less emphysema, and less airway wall thickening, while higher omega-6s and a higher omega 6:3 ratio were associated with worse lung phenotypes. Higher omega-3s and omega-6s were each associated with higher DNAm at cg05575921 in the aryl hydrocarbon receptor repressor gene (AHRR), lower epigenetic smoking scores, and a slower epigenetic pace of aging; the omega 6:3 ratio showed opposite associations. Smoking-related DNAm partially mediated some PUFA- lung phenotype asssociations. Omega-3s showed beneficial direct and mediated effects; some omega-6s showed detrimental direct effects but beneficial mediated effects; and the omega 6:3 ratio showed detrimental direct and mediated effects. For example, direct and AHRR DNAm-mediated effects on FEV1 were 0.0201 and 0.0049 for total omega-3s, -0.0049 and 0.0009 for total omega-6s, and - 0.0074 and - 0.0014 for the omega 6:3 ratio. Replication analysis in LTRC generally showed consistent directions of effects across blood and lung tissue.

conclusionsPUFAs may mitigate smoking-related epigenetic alterations, with omega-3s particularly associated with better lung outcomes. These findings have implications for PUFA-focused precision nutrition strategies in high-risk populations.

Indexed as

EmphysemaEpigeneticsLung functionPolyunsaturated fatty acidsSmoking

Identifiers

PMID42414885
PMCPMC13613738

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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.