Imputed DNA methylation outperforms measured loci associations with smoking and chronological age

Anne Richmond; Jure Mur; Sarah Elizabeth Harris; Janie Corley; Hannah R. Elliott; Christopher N. Foley; Eilis J. Hannon; Zhana Kuncheva; Josine L. Min; Mahdi Moqri; Magatte Ndiaye; Benjamin B. Sun; Catalina A. Vallejos; Kejun Ying; Vadim N. Gladyshev; Simon R Cox; Daniel L. McCartney; Riccardo Emilio Marioni

doi:10.1101/2024.09.05.611501

GeneticsbioRxivSep 5, 2024

Preprint

Imputed DNA methylation outperforms measured loci associations with smoking and chronological age

Anne Richmond iD, Jure Mur iD, Sarah Elizabeth Harris iD, Janie Corley iD, Hannah R. Elliott iD, Christopher N. Foley iD, Eilis J. Hannon iD, Zhana Kuncheva iD, Josine L. Min iD, Mahdi Moqri iD, Magatte Ndiaye iD, Benjamin B. Sun iD, Catalina A. Vallejos iD, Kejun Ying iD, Vadim N. Gladyshev iD, Simon R Cox, Daniel L. McCartney iD, Riccardo Emilio Marioni iD

Abstract

Multi-locus signatures of blood-based DNA methylation are well-established biomarkers for lifestyle and health outcomes. Here, we focus on two CpGs that are strongly associated with age and smoking behaviour. Imputing these loci via epigenome-wide CpGs results in stronger associations with outcomes in external datasets compared to directly measured CpGs. If extended epigenome-wide, CpG imputation could augment historic arrays and recently-released, inexpensive but lower-content arrays, thereby yielding better-powered association studies.

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