Bayesian reassessment of the epigenetic architecture of complex traits Trejo Banos, D McCartney, DL Patxot, M Anchieri, L Battram, T Christiansen, C Costeira, R Walker, RM Morris, SW Campbell, A Zhang, Q Porteous, DJ McRae, AF Wray, NR Visscher, PM Haley, CS Evans, KL Deary, IJ McIntosh, AM Hemani, G Bell, JT Marioni, RE Robinson, Matthew Richard ; https://orcid.org/0000-0001-8982-8813 ddc:570 Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70–79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3–51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal. Springer Nature 2020 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/7999 https://research-explorer.ista.ac.at/download/7999/8000 Trejo Banos D, McCartney D, Patxot M, et al. Bayesian reassessment of the epigenetic architecture of complex traits. <i>Nature Communications</i>. 2020;11. doi:<a href="https://doi.org/10.1038/s41467-020-16520-1">10.1038/s41467-020-16520-1</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-020-16520-1 info:eu-repo/semantics/altIdentifier/issn/2041-1723 info:eu-repo/semantics/altIdentifier/wos/000541702400004 info:eu-repo/semantics/altIdentifier/pmid/32513961 info:eu-repo/semantics/openAccess