article published yes D Trejo Banos author DL McCartney author M Patxot author L Anchieri author T Battram author C Christiansen author R Costeira author RM Walker author SW Morris author A Campbell author Q Zhang author DJ Porteous author AF McRae author NR Wray author PM Visscher author CS Haley author KL Evans author IJ Deary author AM McIntosh author G Hemani author JT Bell author RE Marioni author Matthew Richard Robinson author E5D42276-F5DA-11E9-8E24-6303E66974250000-0001-8982-8813 MaRo department 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. https://research-explorer.ista.ac.at/download/7999/8000/2020_NatureComm_Bayesian.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Springer Nature2020 eng 2041-1723 32513961 00054170240000410.1038/s41467-020-16520-1 11 https://doi.org/10.1038/s41467-020-19099-9 D. Trejo Banos <i>et al.</i>, “Bayesian reassessment of the epigenetic architecture of complex traits,” <i>Nature Communications</i>, vol. 11. Springer Nature, 2020. D. Trejo Banos, D. McCartney, M. Patxot, L. Anchieri, T. Battram, C. Christiansen, R. Costeira, R. Walker, S. Morris, A. Campbell, Q. Zhang, D. Porteous, A. McRae, N. Wray, P. Visscher, C. Haley, K. Evans, I. Deary, A. McIntosh, G. Hemani, J. Bell, R. Marioni, M.R. Robinson, Nature Communications 11 (2020). 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> Trejo Banos, D., et al. “Bayesian Reassessment of the Epigenetic Architecture of Complex Traits.” <i>Nature Communications</i>, vol. 11, 2865, Springer Nature, 2020, doi:<a href="https://doi.org/10.1038/s41467-020-16520-1">10.1038/s41467-020-16520-1</a>. Trejo Banos, D, DL McCartney, M Patxot, L Anchieri, T Battram, C Christiansen, R Costeira, et al. “Bayesian Reassessment of the Epigenetic Architecture of Complex Traits.” <i>Nature Communications</i>. Springer Nature, 2020. <a href="https://doi.org/10.1038/s41467-020-16520-1">https://doi.org/10.1038/s41467-020-16520-1</a>. Trejo Banos D, McCartney D, Patxot M, Anchieri L, Battram T, Christiansen C, Costeira R, Walker R, Morris S, Campbell A, Zhang Q, Porteous D, McRae A, Wray N, Visscher P, Haley C, Evans K, Deary I, McIntosh A, Hemani G, Bell J, Marioni R, Robinson MR. 2020. Bayesian reassessment of the epigenetic architecture of complex traits. Nature Communications. 11, 2865. Trejo Banos, D., McCartney, D., Patxot, M., Anchieri, L., Battram, T., Christiansen, C., … Robinson, M. R. (2020). Bayesian reassessment of the epigenetic architecture of complex traits. <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-020-16520-1">https://doi.org/10.1038/s41467-020-16520-1</a> 79992020-06-22T11:18:25Z2024-10-09T20:59:38Z