Father’s adolescent body silhouette is associated with offspring asthma, lung function and BMI through DNA methylation

Father’s adolescent body silhouette is associated with offspring asthma, lung function and BMI through DNA methylation

Abstract 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...

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Main Authors: Negusse Tadesse Kitaba, Toril Mørkve Østergaard, Marianne Lønnebotn, Simone Accordini, Francisco Gómez Real, Andrei Malinovschi, Anna Oudin, Bryndis Benediktsdottir, Francisco Javier Callejas González, Leopoldo Palacios Gómez, Mathias Holm, Nils Oskar Jõgi, Shyamali C. Dharmage, Svein Magne Skulstad, Vivi Schlünssen, Cecilie Svanes, John W. Holloway
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08121-9
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Summary:Abstract 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.
ISSN:2399-3642

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