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An epigenome-wide association study of educational attainment (n = 10,767)

By Richard Karlsson Linnér, Riccardo E Marioni, Cornelius A Rietveld, Andrew Simpkin, Neil M Davies, Kyoko Watanabe, Nicola J. Armstrong, Kirsi Auro, Clemens Baumbach, Marc Jan Bonder, Jadwiga Buchwald, Giovanni Fiorito, Khadeeja Ismail, Stella Iurato, Anni Joensuu, Pauliina Karell, Silva Kasela, Jari Lahti, Allan F. McRae, Pooja R Mandaviya, Ilkka Seppälä, Yunzhang Wang, Laura Baglietto, Elisabeth B. Binder, Sarah E Harris, Allison M Hodge, Steve Horvath, Mikko Hurme, Magnus Johannesson, Antti Latvala, Karen A. Mather, Sarah E Medland, Andres Metspalu, Lili Milani, Roger L Milne, Alison Pattie, Nancy L. Pedersen, Annette Peters, Silvia Polidoro, Katri Räikkönen, Gianluca Severi, John M. Starr, Lisette Stolk, Melanie Waldenberger, BIOS Consortium, Johan G. Eriksson, Tõnu Esko, Lude Franke, Christian Gieger, Graham G Giles, Sara Hägg, Pekka Jousilahti, Jaakko Kaprio, Mika Kähönen, Terho Lehtimäki, Nicholas G Martin, Joyce B. C van Meurs, Miina Ollikainen, Markus Perola, Danielle Posthuma, Olli T Raitakari, Perminder S. Sachdev, Erdogan Taskesen, André G. Uitterlinden, Paolo Vineis, Cisca Wijmenga, Margaret J Wright, Caroline Relton, George Davey Smith, Ian J Deary, Philipp D Koellinger, Daniel J Benjamin

Posted 07 Mar 2017
bioRxiv DOI: 10.1101/114637

The epigenome has been shown to be influenced by 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 of 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. While we find that 9 CpG probes are significantly associated with EA, only two remain associated when we restrict the sample to never-smokers. These two 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, their effect sizes on EA are far smaller than the known associations between CpG probes and biologically proximal environmental factors. Two analyses that combine the effects of many probes, polygenic methylation score and epigenetic-clock analyses, both suggest small associations with EA. 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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