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Title: DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function
Authors: Matías-García, Pamela R.
Ward-Caviness, Cavin K.
Raffield, Laura M.
Gao, Xu
Zhang, Yan
Wilson, Rory
Gào, X?n
Nano, Jana
Bostom, Andrew
Colicino, Elena
Correa, Adolfo
Coull, Brent
Eaton, Charles
Hou, Lifang
Just, Allan C.
Kunze, Sonja
Lange, Leslie
Lange, Ethan
Lin, Xihong
Liu, Simin
Nwanaji-Enwerem, Jamaji C.
Reiner, Alex
Shen, Jincheng
Schöttker, Ben
Vokonas, Pantel
Zheng, Yinan
Young, Bessie
Schwartz, Joel
Horvath, Steve
Lu, Ake
Whitsel, Eric A.
Koenig, Wolfgang
Adamski, Jerzy 
Winkelmann, Juliane
Brenner, Hermann
Baccarelli, Andrea A.
Gieger, Christian
Peters, Annette
Franceschini, Nora
Waldenberger, Melanie
Keywords: Aging
DNAm age
Epigenetic age acceleration
Glomerular filtration rate
Kidney function
Serum urate
Issue Date: 2-Jun-2021
Publisher: BioMed Central Ltd
Citation: Matías-García, Pamela R., Ward-Caviness, Cavin K., Raffield, Laura M., Gao, Xu, Zhang, Yan, Wilson, Rory, Gào, X?n, Nano, Jana, Bostom, Andrew, Colicino, Elena, Correa, Adolfo, Coull, Brent, Eaton, Charles, Hou, Lifang, Just, Allan C., Kunze, Sonja, Lange, Leslie, Lange, Ethan, Lin, Xihong, Liu, Simin, Nwanaji-Enwerem, Jamaji C., Reiner, Alex, Shen, Jincheng, Schöttker, Ben, Vokonas, Pantel, Zheng, Yinan, Young, Bessie, Schwartz, Joel, Horvath, Steve, Lu, Ake, Whitsel, Eric A., Koenig, Wolfgang, Adamski, Jerzy, Winkelmann, Juliane, Brenner, Hermann, Baccarelli, Andrea A., Gieger, Christian, Peters, Annette, Franceschini, Nora, Waldenberger, Melanie (2021-06-02). DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function. Clinical Epigenetics 13 (1) : 121. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E?03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang’s 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (? = ? 0.12, 95% CI = [? 0.16, ? 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E?08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (? = 0.12 [0.07, 0.16], p = 2.08E?06). The “first-generation” clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease. © 2021, The Author(s).
Source Title: Clinical Epigenetics
ISSN: 1868-7075
DOI: 10.1186/s13148-021-01082-w
Rights: Attribution 4.0 International
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