DNA methylation signatures of educational attainment
van Dongen J., Bonder MJ., Dekkers KF., Nivard MG., van Iterson M., Willemsen G., Beekman M., van der Spek A., van Meurs JBJ., Franke L., Heijmans BT., van Duijn CM., Slagboom PE., Boomsma DI., Heijmans BT., ’t Hoen PAC., van Meurs J., Isaacs A., Jansen R., Franke L., Boomsma DI., Pool R., van Dongen J., Hottenga JJ., van Greevenbroek MM., Stehouwer CDA., van der Kallen CJH., Schalkwijk CG., Wijmenga C., Franke L., Zhernakova S., Tigchelaar EF., Slagboom PE., Beekman M., Deelen J., van Heemst D., Veldink JH., van den Berg LH., van Duijn CM., Hofman BA., Isaacs A., Uitterlinden AG., van Meurs J., Jhamai PM., Verbiest M., Suchiman HED., Verkerk M., van der Breggen R., van Rooij J., Lakenberg N., Mei H., van Iterson M., van Galen M., Bot J., Zhernakova DV., Jansen R., van’t Hof P., Deelen P., Nooren I., Heijmans BT., Moed M., Franke L., Vermaat M., Luijk R., Bonder MJ., van Iterson M., Deelen P., van Dijk F., Arindrarto W., Kielbasa SM., Swertz MA., van Zwet EW., Jansen R., Hoen PB., Heijmans BT.
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.