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An epigenome-wide association study meta-analysis of educational attainment.
R Karlsson Linnér1,2, R E Marioni3,4, C A Rietveld2,5,6
1Department of Complex Trait Genetics, Vrije Universiteit Amsterdam, Center for Neurogenomics and Cognitive Research, Amsterdam, The Netherlands.
Molecular Psychiatry
|November 1, 2017
Summary
Epigenetic modifications, specifically CpG methylation, show weak associations with educational attainment (EA). These links are largely explained by smoking, questioning the profound impact of biologically distal environmental factors on the epigenome.
Area of Science:
- Epigenetics
- Human Genetics
- Environmental Health
Background:
- The epigenome is influenced by biological and environmental factors, including disease, smoking, alcohol, and body mass index.
- A perception exists that environmental factors profoundly impact the epigenome, yet evidence for biologically distal factors is limited.
- Educational attainment (EA) represents a significant life-shaping experience and a biologically distal environmental factor.
Purpose of the Study:
- To investigate the associations between epigenetic modifications (CpG methylation) and educational attainment (EA) in humans.
- To assess the influence of a biologically distal environmental factor, EA, on the epigenome.
Main Methods:
- Conducted an epigenome-wide association study (EWAS) meta-analysis of EA.
- Utilized data from 27 cohort studies, totaling 10,767 individuals.
- Performed robustness and sensitivity analyses, including subset analysis of never-smokers and examination of correlations with smoking.
Main Results:
- Identified nine CpG probes significantly associated with EA.
- Robustness analyses revealed all nine probes were previously associated with smoking.
- Sensitivity analyses in never-smokers yielded two associations linked to maternal smoking during pregnancy, suggesting confounding.
- Effect sizes for EA associations were considerably smaller than those for proximal factors (alcohol, BMI, smoking, maternal smoking).
- Combined methylation probe analyses indicated small EA associations highly correlated with smoking effects.
Conclusions:
- The observed epigenetic associations with educational attainment are weak and largely confounded by smoking.
- These findings challenge the hypothesis that biologically distal environmental factors have substantial effects on the human epigenome.
- Further research is needed to clarify the complex interplay between environmental factors, epigenetics, and life-shaping experiences.
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