Abstract
BackgroundAccumulating evidence links paternal adiposity in the periconceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans.MethodsIn the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of coordinated epigenome-wide association studies (EWAS) of paternal prenatal body mass index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 data sets; total n = 4894) and in childhood (6 data sets; total n = 1982).ResultsWe found little evidence of an association at either time point: at all CpGs, the false-discovery-rate-adjusted P-values were >0.05. In secondary sex-stratified analyses, we found just four CpGs for which there was robust evidence of an association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes.ConclusionOur findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring-blood DNA methylation, even at imprinted regions.
Highlights
Accumulating evidence links paternal exposures in the periconceptional period to offspring health outcomes.[1,2,3] Results from animal studies support a causal role for ‘paternal effects’[4] that are independent of maternal effects.[2]
In a sex-stratified analysis adjusted for maternal body mass index (BMI), we found some evidence of an association between methylation and paternal BMI at seven CpGs in female offspring only (Table 4)
In a previous Pregnancy And Childhood Epigenetics (PACE)-consortium study,[26] we identified 86 cord-blood CpGs associated with maternal BMI in an epigenome-wide association studies (EWAS) meta-analysis across 19 cohorts (9 of which contributed results to the current study)
Summary
Accumulating evidence links paternal exposures in the periconceptional period to offspring health outcomes.[1,2,3] Results from animal studies support a causal role for ‘paternal effects’[4] that are independent of maternal effects.[2] Whereas prenatal maternal effects are most commonly postulated to occur via fetal intrauterine exposure, the suggested biological mechanisms underlying paternal effects[3,5] include germline de novo genetic mutations[6] or epigenetic changes,[7] or alterations in the components or properties of semen.[8]. Methods: In the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of coordinated epigenome-wide association studies (EWAS) of paternal prenatal body mass index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 data sets; total n 1⁄4 4894) and in childhood (6 data sets; total n 1⁄4 1982). To compare our findings to those of other studies, we conducted a systematic
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