Fathers' preconception smoking and offspring DNA methylation.

Autor: Kitaba NT; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, UK., Knudsen GTM; Department of Clinical Sciences, University of Bergen, Bergen, Norway.; Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway., Johannessen A; Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway., Rezwan FI; Department of Computer Science, Aberystwyth University, Aberystwyth, UK., Malinovschi A; Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden., Oudin A; Section of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden., Benediktsdottir B; Department of Allergy, Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Martino D; Wal-Yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia., González FJC; Department of Pulmonology, Albacete University Hospital Complex, Albacete, Spain., Gómez LP; El Torrejón Health Centre, Andalusian Health Service, Huelva, Spain., Holm M; Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden., Jõgi NO; Department of Clinical Sciences, University of Bergen, Bergen, Norway.; Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway., Dharmage SC; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia., Skulstad SM; Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway., Watkins SH; University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK., Suderman M; University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK., Gómez-Real F; Department of Clinical Sciences, University of Bergen, Bergen, Norway.; Department of Gynaecology and Obstetrics, Haukeland University Hospital, Bergen, Norway., Schlünssen V; Department of Public Health, Work, Environment and Health, Danish Ramazzini Centre, Aarhus University Denmark, Aarhus, Denmark.; National Research Center for the Working Environment, Copenhagen, Denmark., Svanes C; Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.; Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway., Holloway JW; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, UK. J.W.Holloway@soton.ac.uk.; NIHR Southampton Biomedical Research Center, University Hospitals Southampton, Southampton, UK. J.W.Holloway@soton.ac.uk.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2023 Aug 31; Vol. 15 (1), pp. 131. Date of Electronic Publication: 2023 Aug 31.
DOI: 10.1186/s13148-023-01540-7
Abstrakt: Background: Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are, however, limited. We aim to identify epigenetic marks in offspring associated with father's preconception smoking.
Methods: We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort (7-50 years) on father's any preconception smoking (n = 875 offspring) and father's pubertal onset smoking < 15 years (n = 304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, own smoking and maternal smoking. EWAS of maternal and offspring personal smoking were performed for comparison. Father's smoking-associated dmCpGs were checked in subpopulations of offspring who reported no personal smoking and no maternal smoking exposure.
Results: Father's smoking commencing preconception was associated with methylation of blood DNA in offspring at two cytosine-phosphate-guanine sites (CpGs) (false discovery rate (FDR) < 0.05) in PRR5 and CENPP. Father's pubertal onset smoking was associated with 19 CpGs (FDR < 0.05) mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (p < 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. Father's smoking-associated sites did not overlap with dmCpGs identified in EWAS of personal and maternal smoking (FDR < 0.05), and all sites remained significant (p < 0.05) in analyses of offspring with no personal smoking and no maternal smoking exposure.
Conclusion: Father's preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underlie epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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