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

R Karlsson Linnér; R E Marioni; C A Rietveld; A J Simpkin; M Davis; Nicola J Armstrong; K Auro; C Baumbach; M J Bonder; J Buchwald; G Fiorito; K Ismail; S Iurato; A Joensuu; P Karell; S Kasela; J Lahti; A F Mcrae; P R Mandaviya; I Seppälä; Y. Wang; L Baglietto; E B Binder; Sarah Harris; Mary Hodge; S Horvath; M Hurme; M Johannesson; A Latvala; K A Mather; S E Medland; A Metspalu; L Milani; Roger L Milne; A Pattie; N L Pedersen; A Peters; S Polidoro; K Räikkönen; G Severi; J M Starr; L Stolk; M Waldenberger; J G Eriksson; T Esko; L Franke; C Gieger; G G Giles; S Hägg; P Jousilahti; J Kaprio; M Kähönen; T Lehtimäki; N G Martin; J B C Van Meurs; M Ollikainen; M Perola; D Posthuma; O T Raitakari; P S Sachdev; E Taskesen; A G Uitterlinden; P Vineis; C Wijmenga; M J Wright; C Relton; G Davey Smith; I J Deary; P D Koellinger; D J Benjamin

doi:10.1038/mp.2017.210

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

R Karlsson Linnér, R E Marioni, C A Rietveld, A J Simpkin, M Davis, Nicola J Armstrong, K Auro, C Baumbach, M J Bonder, J Buchwald, G Fiorito, K Ismail, S Iurato, A Joensuu, P Karell, S Kasela, J Lahti, A F Mcrae, P R Mandaviya, I SeppäläY. Wang, L Baglietto, E B Binder, Sarah Harris, Mary Hodge, S Horvath, M Hurme, M Johannesson, A Latvala, K A Mather, S E Medland, A Metspalu, L Milani, Roger L Milne, A Pattie, N L Pedersen, A Peters, S Polidoro, K Räikkönen, G Severi, J M Starr, L Stolk, M Waldenberger, J G Eriksson, T Esko, L Franke, C Gieger, G G Giles, S Hägg, P Jousilahti, J Kaprio, M Kähönen, T Lehtimäki, N G Martin, J B C Van Meurs, M Ollikainen, M Perola, D Posthuma, O T Raitakari, P S Sachdev, E Taskesen, A G Uitterlinden, P Vineis, C Wijmenga, M J Wright, C Relton, G Davey Smith, I J Deary, P D Koellinger, D J Benjamin

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Journal	Molecular Psychiatry
Early online date	31 Oct 2017
DOIs	https://doi.org/10.1038/mp.2017.210
Publication status	E-pub ahead of print - 31 Oct 2017

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mp2017210aFinal published version, 1.88 MBLicence: CC BY

Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III
Wardlaw, J., Bastin, M. & Deary, I.
MRC
1/05/15 → 30/04/19
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I., Gale, C., Holmes, M., Logie, P., Maclullich, A., Porteous, D., Seckl, J., Starr, J., Wardlaw, J. & Okely, J.
1/09/13 → 31/08/19
Project: Research

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Karlsson Linnér, R., Marioni, R. E., Rietveld, C. A., Simpkin, A. J., Davis, M., Armstrong, N. J., Auro, K., Baumbach, C., Bonder, M. J., Buchwald, J., Fiorito, G., Ismail, K., Iurato, S., Joensuu, A., Karell, P., Kasela, S., Lahti, J., Mcrae, A. F., Mandaviya, P. R., ... Benjamin, D. J. (2017). An epigenome-wide association study meta-analysis of educational attainment. Molecular Psychiatry. Advance online publication. https://doi.org/10.1038/mp.2017.210

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title = "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 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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Karlsson Linnér, R, Marioni, RE, Rietveld, CA, Simpkin, AJ, Davis, M, 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, S, Hodge, M, 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, Hägg, 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, Davey Smith, G, Deary, IJ, Koellinger, PD & Benjamin, DJ 2017, 'An epigenome-wide association study meta-analysis of educational attainment', Molecular Psychiatry. https://doi.org/10.1038/mp.2017.210

TY - JOUR

T1 - An epigenome-wide association study meta-analysis of educational attainment

AU - Karlsson Linnér, R

AU - Marioni, R E

AU - Rietveld, C A

AU - Simpkin, A J

AU - Davis, M

AU - Armstrong, Nicola J

AU - Auro, K

AU - Baumbach, C

AU - Bonder, M J

AU - Buchwald, J

AU - Fiorito, G

AU - Ismail, K

AU - Iurato, S

AU - Joensuu, A

AU - Karell, P

AU - Kasela, S

AU - Lahti, J

AU - Mcrae, A F

AU - Mandaviya, P R

AU - Seppälä, I

AU - Wang, Y.

AU - Baglietto, L

AU - Binder, E B

AU - Harris, Sarah

AU - Hodge, Mary

AU - Horvath, S

AU - Hurme, M

AU - Johannesson, M

AU - Latvala, A

AU - Mather, K A

AU - Medland, S E

AU - Metspalu, A

AU - Milani, L

AU - Milne, Roger L

AU - Pattie, A

AU - Pedersen, N L

AU - Peters, A

AU - Polidoro, S

AU - Räikkönen, K

AU - Severi, G

AU - Starr, J M

AU - Stolk, L

AU - Waldenberger, M

AU - Eriksson, J G

AU - Esko, T

AU - Franke, L

AU - Gieger, C

AU - Giles, G G

AU - Hägg, S

AU - Jousilahti, P

AU - Kaprio, J

AU - Kähönen, M

AU - Lehtimäki, T

AU - Martin, N G

AU - Van Meurs, J B C

AU - Ollikainen, M

AU - Perola, M

AU - Posthuma, D

AU - Raitakari, O T

AU - Sachdev, P S

AU - Taskesen, E

AU - Uitterlinden, A G

AU - Vineis, P

AU - Wijmenga, C

AU - Wright, M J

AU - Relton, C

AU - Davey Smith, G

AU - Deary, I J

AU - Koellinger, P D

AU - Benjamin, D J

N1 - Gold OA

PY - 2017/10/31

Y1 - 2017/10/31

N2 - 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.

AB - 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.

U2 - 10.1038/mp.2017.210

DO - 10.1038/mp.2017.210

M3 - Article

SN - 1359-4184

JO - Molecular Psychiatry

JF - Molecular Psychiatry

ER -

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

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Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

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