(OR06-05-26) Polyunsaturated Fatty Acid Associations With Epigenetic Variation in the Respiratory Epithelium

Saturday, July 25, 2026

10:48 AM - 11:00 AM ET

Location: National Harbor 4-5

Presenting Author(s)

Bonnie K. Patchen, PhD, RD (she/her/hers)

Postdoctoral Research Fellow
Brigham and Women's Hospital
Boston, Massachusetts, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

EP

E. Kate Phillips

Brigham and Women's Hospital, United States
WS

Woei-Yuh Saw

Brigham and Women's Hospital; Harvard Medical School, United States
MC

Michael Cho

Brigham and Women's Hospital; Harvard Medical School, United States
BL

Bruce D. Levy

Brigham and Women's Hospital; Harvard Medical School, United States
ES

Edwin K. Silverman

Brigham and Women's Hospital; Harvard Medical School, United States
DH

Dana B. Hancock

Research Triangle Institute International, United States
PC

Patricia A. Cassano

Cornell University; Weill Cornell Medicine, United States
DD

Dawn L. DeMeo

Brigham and Women's Hospital; Harvard Medical School, United States

Disclosure(s):

Bonnie K. Patchen, PhD, RD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Polyunsaturated fatty acids (PUFAs) have epigenetic effects and may protect against environmental toxins. We aimed to characterize PUFA associations with DNA methylation (DNAm) in the respiratory epithelium, a key interface between the external environment and the lungs, and investigate interactions with smoking.

Methods: We evaluated PUFA biomarker and nasal epithelium DNAm data from 181 participants with a history of smoking from the Genetic Epidemiology of COPD (COPDGene) Study. Plasma PUFAs were quantified by gas chromatography-mass spectrometry. Nasal epithelium DNAm was assayed with the Infinium EPIC array. Differentially methylated regions (DMRs) associated with total omega-3 (N3), total omega-6 (N6) and ratio of omega 6:3 (N6:N3) PUFAs, with and without interaction terms for PUFA x DNAm at the AHRR gene, an epigenetic marker of current smoking, were evaluated with the R package DMRcate. Models were adjusted for age, sex, ancestry PCs and smoking pack-years. Pathway enrichment was evaluated with the R package missMethyl.

Results: In models of PUFA main effects we identified 130 DMRs for N3 and 288 DMRs for N6:N3; no DMRs were found for N6. Pathway analysis revealed enrichment for immune system signaling and regulation, viral infection, and cancer pathways. In models of PUFA x smoking interactions, we found 5 DMRs for N3, 7 DMRs for N6, and 266 DMRs for N6:N3. While some DMRs for PUFA main and interaction effects overlapped (1 for N3, 40 for N6:N3 ratio), 237 were unique to smoking interactions. Pathway analysis of DMRs for smoking interactions showed enrichment for asthma and other inflammatory diseases and highlighted key immune system genes including IL10, which encodes the anti-inflammatory cytokine Interleukin-10, and FCER1G, which encodes a subunit of the IgE receptor, a critical mediator of allergic inflammatory signaling.

Conclusions: PUFAs may modulate the respiratory epithelium epigenetic landscape, including through interactions with smoking, which may play a role in immune system regulation, response to infection, and chronic inflammatory airway disease.

Funding Sources: Research reported in this abstract was supported by the NIH and NHLBI. The COPDGene study is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee.