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Comprehensive evaluation of smoking exposures and their interactions on DNA methylation.
Hoang, Thanh T; Lee, Yunsung; McCartney, Daniel L; Kersten, Elin T G; Page, Christian M; Hulls, Paige M; Lee, Mikyeong; Walker, Rosie M; Breeze, Charles E; Bennett, Brian D; Burkholder, Adam B; Ward, James; Brantsæter, Anne Lise; Caspersen, Ida H; Motsinger-Reif, Alison A; Richards, Marie; White, Julie D; Zhao, Shanshan; Richmond, Rebecca C; Magnus, Maria C; Koppelman, Gerard H; Evans, Kathryn L; Marioni, Riccardo E; Håberg, Siri E; London, Stephanie J.
Affiliation
  • Hoang TT; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA; Department of Pediatrics, Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Dan L. Duncan Comprehensive Can
  • Lee Y; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
  • McCartney DL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK.
  • Kersten ETG; University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Dept. of Pediatric Pulmonology and Pediatric Allergy, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the Netherlands.
  • Page CM; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Department of Physical Health and Ageing, Division for Physical and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Hulls PM; Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2BN, UK; MRC Integrative Epidemiology Unit at University of Bristol, BS8 2BN, UK.
  • Lee M; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
  • Walker RM; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK; School of Psycholog
  • Breeze CE; UCL Cancer Institute, University College London, Paul O'Gorman Building, London, UK; Altius Institute for Biomedical Sciences, Seattle, WA, USA.
  • Bennett BD; Department of Health and Human Services, Integrative Bioinformatics Support Group, National Institutes of Health, Research Triangle Park, NC, USA.
  • Burkholder AB; Department of Health and Human Services, Office of Environmental Science Cyberinfrastructure, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
  • Ward J; Department of Health and Human Services, Integrative Bioinformatics Support Group, National Institutes of Health, Research Triangle Park, NC, USA.
  • Brantsæter AL; Department of Food Safety, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Caspersen IH; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Motsinger-Reif AA; Department of Health and Human Services, Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
  • Richards M; Westat, Durham, NC, USA.
  • White JD; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA; GenOmics and Translational Research Center, Analytics Practice Area, RTI International, Research Triangle Park, NC, USA.
  • Zhao S; Department of Health and Human Services, Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
  • Richmond RC; Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2BN, UK; MRC Integrative Epidemiology Unit at University of Bristol, BS8 2BN, UK.
  • Magnus MC; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Koppelman GH; University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Dept. of Pediatric Pulmonology and Pediatric Allergy, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the Netherlands.
  • Evans KL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK.
  • Marioni RE; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK.
  • Håberg SE; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
  • London SJ; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Electronic address: london2@niehs.nih.gov.
EBioMedicine ; 100: 104956, 2024 Feb.
Article in En | MEDLINE | ID: mdl-38199042
ABSTRACT

BACKGROUND:

Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of differential methylation from in utero smoking exposure, and effects of environmental tobacco smoke (ETS).

METHODS:

We meta-analysed data from up to 15,014 adults across 5 cohorts with DNA methylation measured in blood using Illumina's EPIC array for current smoking (2560 exposed), quit < 1 year (500 exposed), in utero (286 exposed), and ETS exposure (676 exposed). We also evaluated the interaction of current smoking with sex or diet (fibre, folate, and vitamin C).

FINDINGS:

Using false discovery rate (FDR < 0.05), 65,857 CpGs were differentially methylated in relation to current smoking, 4025 with recent quitting, 594 with in utero exposure, and 6 with ETS. Most current smoking CpGs attenuated within a year of quitting. CpGs related to in utero exposure in adults were enriched for those previously observed in newborns. Differential methylation by current smoking at 4-71 CpGs may be modified by sex or dietary intake. Nearly half (35-50%) of differentially methylated CpGs on the 450 K array were associated with blood gene expression. Current smoking and in utero smoking CpGs implicated 3049 and 1067 druggable targets, including chemotherapy drugs.

INTERPRETATION:

Many smoking-related methylation sites were identified with Illumina's EPIC array. Most signals revert to levels observed in never smokers within a year of cessation. Many in utero smoking CpGs persist into adulthood. Smoking-related druggable targets may provide insights into cancer treatment response and shared mechanisms across smoking-related diseases.

FUNDING:

Intramural Research Program of the National Institutes of Health, Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, Chief Scientist Office of the Scottish Government Health Directorates and the Scottish Funding Council, Medical Research Council UK and the Wellcome Trust.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tobacco Smoke Pollution / Smoking Cessation Type of study: Prognostic_studies Limits: Adult / Humans / Newborn Language: En Journal: EBioMedicine Year: 2024 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tobacco Smoke Pollution / Smoking Cessation Type of study: Prognostic_studies Limits: Adult / Humans / Newborn Language: En Journal: EBioMedicine Year: 2024 Document type: Article