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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.

SUBMITTER: Karlsson Linner R

PROVIDER: S-EPMC6372242 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

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

Molecular psychiatry 20171031 12

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 methylati ...[more]

PMID: 29086770

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Project description:Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

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

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

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