An epigenome-wide association study meta-analysis of educational attainment

Abstract

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption, and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here, we provide evidence on the associations between epigenetic modifications—in our case, CpG methylation—and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10,767 individuals. We find 9 CpG probes significantly associated with EA. However, robustness analyses show that all 9 probes have previously been found to be associated with smoking. Only 2 associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these 2 probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, BMI, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Developments in molecular epidemiology of aging

“…To meet this challenge, investigators and funders have formed global consortia and invested in massive collaborative research endeavors to achieve samples of tens or hundreds of thousands. In aging research, the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium, which has conducted a large epigenome-wide association study (EWAS) on educational attainment including epigenetic clock analyses [71], as alluded to above, is an example.…”

Epigenetic prediction of complex traits and death

“…Through large meta-analysis projects, methylation signals at individual CpG sites have been associated with educational attainment, smoking, alcohol consumption, cholesterol levels, and BMI [ 5 – 13 ]. Such studies have also used methylation predictors (from a combination of CpG sites) to predict the phenotype of interest in independent cohorts.…”

Cognitive and brain development is independently influenced by socioeconomic status and polygenic scores for educational attainment

“…Reward signals and selected epigenetic markers have indeed been discussed as possible malleable neurobiological markers being associated with cognitive capacity in adolescents 22 . However, to date, one epigenome-wide analysis for educational attainment casts doubt on possible epigenetic markers for educational attainment 23 . The global result we observed could come from one or several factors with a global impact or be the result of several regional effects that together impact most of the cortex with wideranging behavioral outcomes 24 .…”