Abstract
Educational attainment is a key behavioural measure in studies of cognitive and physical health, and socioeconomic status. We measured DNA methylation at 410,746 CpGs (N = 4152) and identified 58 CpGs associated with educational attainment at loci characterized by pleiotropic functions shared with neuronal, immune and developmental processes. Associations overlapped with those for smoking behaviour, but remained after accounting for smoking at many CpGs: Effect sizes were on average 28% smaller and genome-wide significant at 11 CpGs after adjusting for smoking and were 62% smaller in never smokers. We examined sources and biological implications of education-related methylation differences, demonstrating correlations with maternal prenatal folate, smoking and air pollution signatures, and associations with gene expression in cis, dynamic methylation in foetal brain, and correlations between blood and brain. Our findings show that the methylome of lower-educated people resembles that of smokers beyond effects of their own smoking behaviour and shows traces of various other exposures.
Highlights
Educational attainment correlates across time and countries with prosperity, and across individuals within populations with cognitive functioning,[1] personality,[2] physical and mental health,[3] and socioeconomic conditions across the lifespan.[4]
By employing an epigenome-wide association approach in a large consortium study of adult subjects from the Netherlands with harmonized data for educational attainment, we have identified methylation sites significantly associated with educational attainment
This suggests that factors in the childhood environment or genetic factors may account for part of the association between educational attainment observed in the entire population
Summary
Educational attainment correlates across time and countries with prosperity, and across individuals within populations with cognitive functioning,[1] personality,[2] physical and mental health,[3] and socioeconomic conditions across the lifespan.[4] A recent genome-wide association study (GWAS) reported an association between educational attainment and SNPs at 74 loci.[5] The findings pointed at biological pathways that contribute to individual differences in educational attainment in human populations: A large proportion of SNPs was associated with gene expression in the foetal brain and the functions and expression patterns of the loci pointed at an involvement in neural development processes. Throughout development and the adult lifespan, gene expression is regulated by epigenetic mechanisms, such as DNA methylation. DNA methylation plays a crucial role in brain development and learning,[6,7] and is increasingly recognized as an important mechanism that mediates genetic and environmental effects on health. Later life exposures induce changes to the methylome, for example exposure to cigarette smoke.[21,22]
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