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

2024 · doi:10.1101/2024.09.05.611501
preprint OA: gold CC-BY-4.0
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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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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. Competing Interest Statement R.E.M is an advisor to the Epigenetic Clock Development Foundation and Optima Partners Ltd. D.L.M. is employed by Optima Partners Ltd in a part-time capacity. The remaining authors declare no competing interests. M.M., K.Y. and V.N.G. have filed patents on measuring aging from DNA methylation.

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License: CC-BY-4.0