Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the pregnancy and childhood epigenetics consortium

Abstract

Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.

What makes clocks tick? Characterizing developmental dynamics of adult epigenetic clock sites

“…Findings were included based on availability in the EWAS Catalog 25 . Prenatal exposures included sustained maternal smoking ( n =2,620 associated sites) 26 , hypertensive disorders ( n =920) 27 , overweight/obesity ( n =159) 28 , body mass index (BMI; n =104) 28 , (pregnancy-related) anxiety ( n =57) 29 , haemoglobin levels ( n =40) 30 , and air pollution exposure (NO 2 , n =24 PM 2.5 , n =6) 31,32 . Altogether,1% of the sites measured on the 450k array have been related to a prenatal exposure.…”

“…The EWAS Catalog includes sites with an association of p <1×10 −04 , yet the inclusion thresholds vary somewhat between the studies. Prenatal exposures included sustained maternal smoking ( n =2,620 associated sites; p -value range=1.35×10 −206 -9.98×10 −05 ) 26 , hypertensive disorders ( n =920; p =1.90×10 −12 -9.90×10 −05 ) 27 , overweight/obesity ( n =159, p =3.80×10 −12 -1.00×10 −07 ) 28 , maternal BMI ( n =104, p =6.00×10 −14 -1.00×10 −07 ) 28 , (pregnancy related) anxiety ( n =57, p =5.33×10 −06 -9.91×10 −05 ) 29 , haemoglobin levels ( n =40, p =1.00×10 −07 -1.40×10 −05 ) 30 , air pollution exposure, measured by NO 2 ( n =24, p =8.65×10 −08 -1.81×10 −05 ) 32 , and PM 2.5 ( n =6, p =8.30×10 −08 -1.80×10 −05 ) 31 .…”

Gynecology Meets Big Data in the Disruptive Innovation Medical Era: State-of-Art and Future Prospects

“…Furthermore, new, emerging biomarkers have been discovered in the fields of genomics and proteomics, like exosomes, which are involved in the cellular cross-talks and related biological processes [16]. Nutrigenomics [17,18], epigenomics [19] and nutriepigenomics [20,21] investigate how dietary habits and nutrition, as well as environmental factors, and their complex, non-linear interactions can finely modulate the human genome and its expression, and impact on human diseases, including gynecological conditions. For instance, a study explored the relationship between folic acid supplementation and one carbon metabolism gene single nucleotide polymorphisms (SNPs) on small-for-gestationalage (SGA) births [17].…”

“…For instance, a study explored the relationship between folic acid supplementation and one carbon metabolism gene single nucleotide polymorphisms (SNPs) on small-for-gestationalage (SGA) births [17]. Other studies assessed the association between pregnancy and childhood epigenetics [19,20].…”