Evidence map›Paper›PMID 37649101›Full record

ArticleClinical epigenetics2023

Fathers' preconception smoking and offspring DNA methylation.

Negusse Tadesse Kitaba, Gerd Toril Mørkve Knudsen, Ane Johannessen, Faisal I Rezwan, Andrei Malinovschi, Anna Oudin, Bryndis Benediktsdottir, David Martino, Francisco Javier Callejas González, Leopoldo Palacios Gómez and 10 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 14 institutions in 7 countries.

Negusse Tadesse Kitaba *Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, UK.
Gerd Toril Mørkve Knudsen *Department of Clinical Sciences, University of Bergen, Bergen, Norway.
Ane JohannessenCentre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Faisal I RezwanDepartment of Computer Science, Aberystwyth University, Aberystwyth, UK.
Andrei MalinovschiDepartment of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden.
Anna OudinSection of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Bryndis BenediktsdottirDepartment of Allergy, Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland.
David MartinoWal-Yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Australia.
Francisco Javier Callejas GonzálezDepartment of Pulmonology, Albacete University Hospital Complex, Albacete, Spain.
Leopoldo Palacios GómezEl Torrejón Health Centre, Andalusian Health Service, Huelva, Spain.
Mathias HolmOccupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Nils Oskar JõgiDepartment of Clinical Sciences, University of Bergen, Bergen, Norway.
Shyamali C DharmageCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Svein Magne SkulstadDepartment of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.
Sarah H WatkinsUniversity of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK.
Matthew SudermanUniversity of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK.
Francisco Gómez-RealDepartment of Clinical Sciences, University of Bergen, Bergen, Norway.
Vivi SchlünssenDepartment of Public Health, Work, Environment and Health, Danish Ramazzini Centre, Aarhus University Denmark, Aarhus, Denmark.
Cecilie Svanes *Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.
John W Holloway *Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, UK. J.W.Holloway@soton.ac.uk.
University of Bergen · NOHaukeland University Hospital · NOAberystwyth University · GBAndalusian Health Service · ESDanish Ramazzini Center · DKMRC Integrative Epidemiology UnitNational University Hospital of Iceland · ISUmeå University · SEUniversity of Bristol · GBUniversity of Gothenburg · SEUniversity of Melbourne · AUUniversity of Southampton · GBUniversity of Western Australia · AUUppsala University · SE

Funding

Medical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_19009Medical Research Council MC_UU_00032/4Medical Research Council MC_UU_12013/2
6 · The paper itself

Abstract

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.

Indexed as

AsthmaDNA MethylationChromosomal Proteins, Non-HistoneCytosineEpigenesis, GeneticGuanineHumansMaleSmokingTobacco SmokingChromosomal Proteins, Non-HistoneCytosineGuanineNCAPG2 protein, humanDNA methylationEpigeneticEpigenome-wide association studyPaternal effectsPreconceptionRHINESSATobacco smoke

Identifiers

PMID37649101
PMCPMC10469907
OpenAlexW4386269695

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.