A1 Refereed original research article in a scientific journal

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




AuthorsLinner RK, Marioni RE, Rietveld CA, Simpkin AJ, Davies NM, Watanabe K, Armstrong NJ, Auro K, Baumbach C, Bonder MJ, Buchwald J, Fiorito G, Ismail K, Iurato S, Joensuu A, Karell P, Kasela S, Lahti J, Mcrae AF, Mandaviya PR, Seppälä I, Wang Y, Baglietto L, Binder EB, Harris SE, Hodge AM, Horvath S, Hurme M, Johannesson M, Latvala A, Mather KA, Medland SE, Metspalu A, Milani L, Milne RL, Pattie A, Pedersen NL, Peters A, Polidoro S, Räikkönen K, Severi G, Starr JM, Stolk L, Waldenberger M, Eriksson JG, Esko T, Franke L, Gieger C, Giles GG, Hagg S, Jousilahti P, Kaprio J, Kähönen M, Lehtimäki T, Martin NG, van Meurs JBC, Ollikainen M, Perola M, Posthuma D, Raitakari OT, Sachdev PS, Taskesen E, Uitterlinden AG, Vineis P, Wijmenga C, Wright MJ, Relton C, Smith GD, Deary IJ, Koellinger PD, Benjamin DJ

PublisherNATURE PUBLISHING GROUP

Publication year2017

JournalMolecular Psychiatry

Journal name in sourceMOLECULAR PSYCHIATRY

Journal acronymMOL PSYCHIATR

Volume22

Issue12

First page 1680

Last page1690

Number of pages11

ISSN1359-4184

eISSN1476-5578

DOIhttps://doi.org/10.1038/mp.2017.210

Web address http://www.nature.com/articles/mp2017210

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/27849463


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 nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two 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, body mass index, 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.

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