Fathers' preconception smoking and offspring DNA methylation

Area of Science:

• Epigenetics
• Human Genetics
• Environmental Health

Background:

• Experimental studies suggest paternal exposures can epigenetically impact offspring respiratory health across generations.
• Human studies on paternal smoking's intergenerational epigenetic effects are limited.
• This study investigates epigenetic marks in offspring linked to father's preconception smoking.

Purpose of the Study:

• To identify specific epigenetic marks (DNA methylation) in offspring associated with paternal preconception smoking.
• To explore the association between paternal pubertal onset smoking and offspring epigenetics.
• To examine if these epigenetic changes correlate with offspring health outcomes.

Main Methods:

• Epigenome-wide association studies (EWAS) were conducted on the RHINESSA cohort.
• DNA methylation was analyzed using Infinium MethylationEPIC Beadchip arrays.
• Statistical adjustments were made for offspring age, personal smoking, and maternal smoking.

Main Results:

• Paternal preconception smoking was associated with differential methylation at two CpG sites (PRR5, CENPP) in offspring blood DNA.
• Paternal pubertal smoking (<15 years) associated with 19 differentially methylated CpGs across 14 genes.
• These methylation changes were linked to offspring asthma, wheezing, weight, and BMI, and enriched in gene ontology pathways for gene expression regulation, inflammation, and innate immunity.

Conclusions:

• Paternal preconception smoking, especially during puberty, is associated with offspring DNA methylation.
• Epigenetic mechanisms may explain epidemiological links between paternal smoking and increased offspring risk for asthma, low lung function, and obesity.
• Findings highlight the potential for paternal lifestyle to influence offspring health through epigenetic inheritance.