Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood

Noor, Nudrat; Rifas‐Shiman, Sheryl L.; Hui, Pei; Dreyfuss, Jonathan M.; Oken, Emily; Hivert, Marie‐France; James‐Todd, Tamarra; Patti, Mary‐Elizabeth; Isganaitis, Elvira

doi:10.1001/jamanetworkopen.2019.16777

Cited by 44 publications

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“…This analysis found that methylation at one CpG site, cg19357369 (chr4:2429884), was significantly increased in obese men in sperm and blood (2% higher DNA methylation, P = 8.95 × 10 −8 , Fig 6D ). Finally, we compared our results with those of a previous study, which identified associations between paternal weight and offspring DNA methylation in a sample of 429 father-mother-child triads [ 29 ]. Out of the nine probes at which Noor and colleagues found an association between cord blood DNA methylation and paternal periconceptional BMI, only one showed a nominally significant association in consistent effect direction in the sperm obesity EWAS ( P = 0.028, DNA methylation difference = 6%) and the combined mixed effects model in blood and sperm ( P = 0.01, DNA methylation difference = 4%).…”

Section: Resultsmentioning

confidence: 99%

The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations

et al. 2020

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Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in spermatozoa. We profiled genome-wide DNA methylation using the Illumina MethylationEPIC array in a cross-sectional study of matched human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) males to analyse tissue covariation of DNA methylation, and identify obesity-associated methylomic signatures. We found that DNA methylation signatures of human blood and spermatozoa are highly discordant, and methylation levels are correlated at only a minority of CpG sites (~1%). At the majority of these sites, DNA methylation appears to be influenced by genetic variation. Obesity-associated DNA methylation in blood was not generally reflected in spermatozoa, and obesity was not associated with altered covariation patterns or accelerated epigenetic ageing in the two tissues. However, one cross-tissue obesity-specific hypermethylated site (cg19357369; chr4:2429884; P = 8.95 × 10 −8 ; 2% DNA methylation difference) was identified, warranting replication and further investigation. When compared to a wide range of human somatic tissue samples (n = 5,917), spermatozoa displayed differential DNA methylation across pathways enriched in transcriptional regulation. Overall, human sperm displays a unique DNA methylation profile that is highly discordant to, and practically uncorrelated with, that of matched peripheral blood. We observed that obesity was only nominally associated with differential DNA methylation in PLOS GENETICS

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Section: Resultsmentioning

confidence: 99%

The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations

et al. 2020

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“…In Project Viva (a cohort that also contributed results to our meta-analysis), Noor et al identified nine CpGs where cord blood methylation was associated with periconceptional paternal BMI after adjustment for maternal BMI (20). In our results at birth, we found the same direction of estimated effect at 7/9 CpGs.…”

Section: Resultsmentioning

confidence: 99%

“…In humans, a recent systematic review (13) found conflicting evidence on the association between paternal body mass index (BMI) and offspring birthweight, and some evidence of an association with greater offspring BMI, weight or body fat mass in childhood. A small number of studies have also found links between paternal BMI and sperm or offspring neonatal blood DNA methylation, but these have been based on candidate genes and/or had very limited sample sizes (14)(15)(16)(17)(18)(19)(20).…”

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confidence: 99%

Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

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et al. 2020

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Background: Accumulating evidence links paternal adiposity in the peri-conceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans. Methods and findings: In the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of co-ordinated 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 datasets; total n= 4,894) and in childhood (six datasets; total n = 1,982). We found little evidence of association at either time point: for all CpGs, the False Discovery Rate-adjusted P-values were >0.05. In sex-stratified analyses, we found just four CpGs where there was robust evidence of 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. Conclusion: Our 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.

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“…A strong association between maternal obesity before pregnancy and childhood obesity is reported to be due to a combination of different in utero programming mechanisms [4,6,25]. Paternal obesity might play an additional role through epigenetic alterations, but this needs further confirmation [26]. Since there is also a correlation between current parental obesity and childhood obesity, the actual food and family environment interfere as well [1,3].…”

Section: Discussionmentioning

confidence: 99%

Eating Habits of Children Born after Maternal Bariatric Surgery

et al. 2020

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Mothers who underwent bariatric surgery (BS) before pregnancy have worrisome eating habits, but little is known about the eating habits of their offspring. EFFECTOR is a cross-sectional, long-term follow-up study of 4–11-year-old children born from mothers that underwent bariatric surgery before pregnancy (n = 36), mothers with overweight/obesity (OW/OB) in a control group (n = 71), and mothers with a normal weight (NW) in a second control group (n = 35). Data on anthropometry and on eating habits obtained through a Food Frequency Questionnaire were collected prospectively. The children’s body mass index (BMI) scores significantly correlated with maternal pre-pregnancy BMI. The prevalence of overweight and obesity was the highest in children of the BS group (38.9% vs. 15.5% for children of the OW/OB group and 5.7% for those of the NW group; p = 0.004). Meal-skipping behavior was comparable between the groups. There was no difference in fruit and vegetable consumption. The BS group consumed more low-calorie sweetened beverages compared to the NW group (p = 0.01) but less fruit juice compared to the NW and OW/OB groups (p = 0.01). Our results may indicate a sugar-avoiding behavior in children of the BS group, fitting dietary maternal habits in a strategy to prevent dumping syndrome. In conclusion, maternal pre-pregnancy bariatric surgery does not alter unhealthy eating behaviors and the risk of development of overweight during childhood in their children.

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Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood

Cited by 44 publications

References 47 publications

The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations

The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations

Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

Eating Habits of Children Born after Maternal Bariatric Surgery

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