摘要:
{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 (beta = - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS
附注:
Matias-Garcia, Pamela R Ward-Caviness, Cavin K Raffield, Laura M Gao, Xu Zhang, Yan Wilson, Rory Gao, Xin 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 Schottker, 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 eng P30ES009089/National Institute of Environmental Health Sciences (US) R01ES021733/National Institute of Environmental Health Sciences (US) R01ES025225/National Institute of Environmental Health Sciences (US) P30ES009089, R01ES027747/National Institute of Environmental Health Sciences (US) HHSN268201600018C/HL/NHLBI NIH HHS/ HHSN268201600001C/HL/NHLBI NIH HHS/ HHSN268201600002C/HL/NHLBI NIH HHS/ HHSN268201600003C/HL/NHLBI NIH HHS/ HHSN268201600004C/HL/NHLBI NIH HHS/ R01- MD012765/Foundation for the National Institutes of Health (US) R01-DK117445/Foundation for the National Institutes of Health (US) R21-HL140385/Foundation for the National Institutes of Health (US) R01-ES020836/Foundation for the National Institutes of Health 60442456 BAA23/Foundation for the National Institutes of Health T32 HL129982/HL/NHLBI NIH HHS/ R21-HL140385/Foundation for the National Institutes of Health HHSN268201800013I/MD/NIMHD NIH HHS/ HHSN268201800014I/Tougaloo College (US) HHSN268201800015I/HB/NHLBI NIH HHS/ HHSN268201800010I/University of Mississippi Medical Center (US) HHSN268201800011I/University of Mississippi Medical Center (US) HHSN268201800012I/University of Mississippi Medical Center (US) KL2TR002490/National Center for Advancing Translational Sciences, National Institutes of Health (US) Germany Clin Epigenetics. 2021 Jun 2;13(1):121. doi: 10.1186/s13148-021-01082-w.
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