Bayesian reassessment of the epigenetic architecture of complex traits

Daniel Trejo Banos, Daniel L McCartney, Marion Patxot, Lucas Anchieri, Thomas Battram, Colette Christiansen, Ricardo Costeira, Rosie M Walker, Stewart W Morris, Archie Campbell, Qian Zhang, David J Porteous, Allan F McRae, Naomi R Wray, Peter M Visscher, Chris S Haley, Kathryn L Evans, Ian J Deary, Andrew M McIntosh, Gibran HemaniJordana T Bell, Riccardo E Marioni, Matthew R Robinson

Research output: Contribution to journalArticle (Academic Journal)

Abstract

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.

Original languageEnglish
Pages (from-to)2865
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 8 Jun 2020

Fingerprint Dive into the research topics of 'Bayesian reassessment of the epigenetic architecture of complex traits'. Together they form a unique fingerprint.

  • Cite this

    Trejo Banos, D., McCartney, D. L., Patxot, M., Anchieri, L., Battram, T., Christiansen, C., Costeira, R., Walker, R. M., Morris, S. W., Campbell, A., Zhang, Q., Porteous, D. J., McRae, A. F., Wray, N. R., Visscher, P. M., Haley, C. S., Evans, K. L., Deary, I. J., McIntosh, A. M., ... Robinson, M. R. (2020). Bayesian reassessment of the epigenetic architecture of complex traits. Nature Communications, 11(1), 2865. https://doi.org/10.1038/s41467-020-16520-1