Crynodeb
Background
Early life paternal adverse environment has significant health consequences for the health of his offspring. Children born from father’s who start smoking before age 15 have three-fold risk of developing asthma, lower lung function and increased BMI. We hypothesised that the underlying mechanism could be in part explained by epigenetic programming.
Aim
To identify epigenetic marks in offspring associated with father’s preconception smoking.
Methods
An epigenome-wide association studie (EWAS) in the RHINESSA cohort from six study centres on father’s pubertal smoking <15 years (N=304) on DNA methylation profiled in blood using Illumina Infinium MethylationEPIC arrays. Differentially methylated CpG sites (dmCpGs) were identified using robust regression models adjusting for offspring age, sex, maternal smoking, personal smoking and blood cell type proportions.
Results
Father’s pubertal onset smoking was associated with 19 dmCpGs (FDR <0.05) mapped to 14 genes including genes whose function relate to immune responses (TLR9, CSFR1) and obesity (IRS1, NTRK2). These dmCpGs were hypermethylated and associated with promoter regions capable of gene silencing. Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. dmCpGs associated with paternal smoking were distinct from those associated with maternal smoking in pregnancy.
Conclusions
Father’s preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underly epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity.
Early life paternal adverse environment has significant health consequences for the health of his offspring. Children born from father’s who start smoking before age 15 have three-fold risk of developing asthma, lower lung function and increased BMI. We hypothesised that the underlying mechanism could be in part explained by epigenetic programming.
Aim
To identify epigenetic marks in offspring associated with father’s preconception smoking.
Methods
An epigenome-wide association studie (EWAS) in the RHINESSA cohort from six study centres on father’s pubertal smoking <15 years (N=304) on DNA methylation profiled in blood using Illumina Infinium MethylationEPIC arrays. Differentially methylated CpG sites (dmCpGs) were identified using robust regression models adjusting for offspring age, sex, maternal smoking, personal smoking and blood cell type proportions.
Results
Father’s pubertal onset smoking was associated with 19 dmCpGs (FDR <0.05) mapped to 14 genes including genes whose function relate to immune responses (TLR9, CSFR1) and obesity (IRS1, NTRK2). These dmCpGs were hypermethylated and associated with promoter regions capable of gene silencing. Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. dmCpGs associated with paternal smoking were distinct from those associated with maternal smoking in pregnancy.
Conclusions
Father’s preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underly epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity.
| Iaith wreiddiol | Saesneg |
|---|---|
| Tudalennau (o-i) | 1206 |
| Nifer y tudalennau | 1 |
| Cyfnodolyn | European Respiratory Journal |
| Cyfrol | 60 |
| Rhif cyhoeddi | S66 |
| Dynodwyr Gwrthrych Digidol (DOIs) | |
| Statws | Cyhoeddwyd - 01 Rhag 2022 |