بيانات النشر: Umeå universitet, Avdelningen för hållbar hälsa
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
Department of Clinical Sciences, University of Bergen, 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 Computer Science, Aberystwyth University, Aberystwyth, United Kingdom
Clinical Physiology, Uppsala University, Uppsala, Sweden
Department of Allergy, Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Wal-Yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia
Department of Pulmonology, Albacete University Hospital Complex, Albacete, Spain
El Torrejón Health Centre, Andalusian Health Service, Huelva, Spain
Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway
University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, United Kingdom
Department of Clinical Sciences, University of Bergen, Bergen, Norway; Department of Gynaecology and Obstetrics, Haukeland University Hospital, 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 Occupational Medicine, Haukeland University Hospital, Bergen, Norway; Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; NIHR Southampton Biomedical Research Center, University Hospitals Southampton, Southampton, United Kingdom
نبذة مختصرة : 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 ...
Processing Request
No Comments.