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

Cohort description:measures of early-life behaviour and later psychopathology in the LifeCycle Project — EU Child Cohort Network

Abstract Background: The EU LifeCycle Project was launched in 2017 to combine, harmonise, and analyse data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview over the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. Methods: Data on cognitive, behavioural and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data for ages 0–18+ years, covering domains across a wide range of behavioural and psychopathology indicators and outcomes (including executive function, depression, ADHD and cognition). These data span a unique combination of qualitative data collected through behavioural/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of brain imaging (MRI, foetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. Conclusions: Mental health data harmonized through the LifeCycle project can be used to study life course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease

Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.Peer reviewe