Fathers’ preconception smoking and offspring DNA methylation

Clinical Epigenetics

Research

Shyamali C. Dharmage¹  Ane Johannessen²  Bryndis Benediktsdottir³  Francisco Gómez-Real⁴  Nils Oskar Jõgi⁵  Gerd Toril Mørkve Knudsen⁵  Faisal I. Rezwan⁶  Andrei Malinovschi⁷  Svein Magne Skulstad⁸  Cecilie Svanes⁹  Vivi Schlünssen^1,10  Francisco Javier Callejas González^1,11  Leopoldo Palacios Gómez^1,12  Negusse Tadesse Kitaba^1,13  John W. Holloway^1,14  Mathias Holm^1,15  Anna Oudin^1,16  Matthew Suderman^1,17  Sarah H. Watkins^1,17  David Martino^1,18 

[1] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia;Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway;Department of Allergy, Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland;Faculty of Medicine, University of Iceland, Reykjavik, Iceland;Department of Clinical Sciences, University of Bergen, Bergen, Norway;Department of Gynaecology and Obstetrics, Haukeland University Hospital, Bergen, Norway;Department of Clinical Sciences, University of Bergen, Bergen, Norway;Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway;Department of Computer Science, Aberystwyth University, Aberystwyth, UK;Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden;Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway;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;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;Department of Pulmonology, Albacete University Hospital Complex, Albacete, Spain;El Torrejón Health Centre, Andalusian Health Service, Huelva, Spain;Human Development and Health, Faculty of Medicine, University of Southampton, SO16 6YD, Southampton, UK;Human Development and Health, Faculty of Medicine, University of Southampton, SO16 6YD, Southampton, UK;NIHR Southampton Biomedical Research Center, University Hospitals Southampton, Southampton, UK;Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden;Section of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden;University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK;Wal-Yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia;

关键词: Preconception;    Paternal effects;    Tobacco smoke;    Epigenetic;    Epigenome-wide association study;    DNA methylation;    RHINESSA;   

DOI  :  10.1186/s13148-023-01540-7

 received in 2023-03-10, accepted in 2023-07-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundExperimental 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.MethodsWe 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.ResultsFather’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.ConclusionFather’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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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