Father’s adolescent body silhouette is associated with offspring asthma, lung function and BMI through DNA methylation
Boys' pubertal overweight associates with future offspring's asthma and low lung function. To identify how paternal overweight is associated with offspring's DNA methylation (DNAm), we conducted an epigenome-wide association study of father's body silhouette (FBS) at three timepoints (age 8, voice break and 30) and change in FBS between these times, with offspring DNAm, in the RHINESSA cohort (N = 339). We identified 2005 differentially methylated cytosine-phosphate-guanine (dmCpG) sites (FDR < 0.05), including dmCpGs associated with offspring asthma (119), lung function (178) and BMI (291). Voice break FBS associated with dmCpGs in loci including KCNJ10, FERMT1, NCK2 and WWP1. Change in FBS across sexual maturation associated with DNAm at loci including NOP10, TRRAP, EFHD1, MRPL17 and NORD59A;ATP5B and showed strong correlation in reduced gene expression in loci NAP1L5, ATP5B, ZNF695, ZNF600, VTRNA2-1, SOAT2 and AGPAT2. We identified 24 imprinted genes including: VTRNA2-1, BLCAP, WT1, NAP1L5 and PTPRN2. Identified pathways relate to lipid and glucose metabolism and adipogenesis. Father's overweight at puberty and during reproductive maturation was strongly associated with offspring DNA, suggesting a key role for epigenetic mechanisms in intergenerational transfer from father to offspring in humans. The results support an important vulnerability window in male puberty for future offspring health.
Authors
- Cecilie Svanes (ORCID: https://orcid.org/0000-0001-8512-5192)
- Leopoldo Palacios Gómez
- Trine Østergaard (ORCID: https://orcid.org/0000-0002-0256-5713)
- Nils Oskar Jõgi (ORCID: https://orcid.org/0000-0002-9600-1950)
- Francisco Gómez Real (ORCID: https://orcid.org/0000-0001-5407-3270)
- Andreï Malinovschi (ORCID: https://orcid.org/0000-0002-4098-7765)
- Francisco Javier Callejas González
- Svein Magne Skulstad (ORCID: https://orcid.org/0000-0003-4841-4328)
- John W. Holloway (ORCID: https://orcid.org/0000-0001-9998-0464)
- Anna Oudin
- Negusse Tadesse Kitaba (ORCID: https://orcid.org/0000-0001-7518-9096)
- Vivi Schlünssen (ORCID: https://orcid.org/0000-0003-4915-1734)
- Simone Accordini (ORCID: https://orcid.org/0000-0003-1510-6193)
- Marianne Lønnebotn (ORCID: https://orcid.org/0000-0002-5594-1567)
- Mathias Holm (ORCID: https://orcid.org/0000-0002-9327-5139)
- Shyamali C Dharmage
- Bryndís Benediktsdóttir
Institutions
- University of Verona (IT)
- Uppsala University (SE)
- Andalusian Health Service (ES)
- The University of Melbourne (AU)
- Western Norway University of Applied Sciences (NO)
- Haukeland University Hospital (NO)
- Danish Ramazzini Center (DK)
- National University Hospital of Iceland (IS)
- NIHR Southampton Biomedical Research Centre (GB)
- University of Southampton (GB)
- University of Bergen (NO)
- University of Gothenburg (SE)
- Umeå University (SE)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-05-24
- DOI
- https://doi.org/10.1038/s42003-025-08121-9
- Citations
- 2
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Aarhus Universitet
- European Commission
- Eesti Teadusagentuur
- Universitetet i Bergen
- Norges Forskningsråd
- Sociedad Española de Neumología y Cirugía Torácica
- Astma- och Allergiförbundet
- Medical Research Council
- National Health and Medical Research Council
- Arbejdstilsynet