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

Richmond, A.; Mur, J.; Harris, S.; Corley, J.; Elliott, H. R.; Foley, C. N.; Hannon, E.; Kuncheva, Z.; Min, J.; Moqri, M.; Ndiaye, M.; Sun, B.; Vallejos, C.; Ying, K.; Gladyshev, V. N.; Cox, S. R.; McCartney, D. L.; Marioni, R.

doi:10.1101/2024.09.05.611501

bioRxiv · 10.1101/2024.09.05.611501

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

Richmond, A.·Mur, J.·Harris, S.·Corley, J.·Elliott, H. R.·Foley, C. N.·Hannon, E.·Kuncheva, Z.·Min, J.·Moqri, M.·Ndiaye, M.·Sun, B.·Vallejos, C.·Ying, K.·Gladyshev, V. N.·Cox, S. R.·McCartney, D. L.·Marioni, R.

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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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Richmond, A., Mur, J., Harris, S., Corley, J., Elliott, H. R., Foley, C. N., Hannon, E., Kuncheva, Z., Min, J., Moqri, M., Ndiaye, M., Sun, B., Vallejos, C., Ying, K., Gladyshev, V. N., Cox, S. R., McCartney, D. L., Marioni, R.. 2024-09-10. Imputed DNA methylation outperforms measured loci associations with smoking and chronological age. https://doi.org/10.1101/2024.09.05.611501

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