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GWAS of epigenetic aging rates in blood reveals a critical role for TERT

Authors :
Steve Horvath
Morgan E. Levine
Andrea A. Baccarelli
Allan F. McRae
Massimo Mangino
James D. Stewart
Alexia Cardona
Eric A. Whitsel
Jordana T. Bell
Alexander P. Reiner
Ken K. Ong
Austin Quach
Yun Li
Philip S. Tsao
Nicholas J. Wareham
Brian H. Chen
Riccardo E. Marioni
Luting Xue
Elias Salfati
Joanne M. Murabito
Devin Absher
Abraham Aviv
Daniel Levy
Douglas P. Kiel
Pei-Chien Tsai
Lifang Hou
Toshiko Tanaka
Idil Yet
Naomi R. Wray
Luigi Ferrucci
John R. B. Perry
Roby Joehanes
Ake T. Lu
Ken Raj
Themistocles L. Assimes
Peter M. Visscher
Ian J. Deary
Felix R. Day
Kathryn L. Lunetta
Xue, Luting [0000-0001-6159-1885]
Chen, Brian H [0000-0001-9065-3301]
Joehanes, Roby [0000-0001-5549-9054]
Mangino, Massimo [0000-0002-2167-7470]
McRae, Allan F [0000-0001-5286-5485]
Visscher, Peter M [0000-0002-2143-8760]
Wray, Naomi R [0000-0001-7421-3357]
Whitsel, Eric A [0000-0003-4843-3641]
Day, Felix R [0000-0003-3789-7651]
Apollo - University of Cambridge Repository
Source :
Nature Communications, Nature communications, vol 9, iss 1, Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018), Lu, A T, Xue, L, Salfati, E L, Chen, B H, Ferrucci, L, Levy, D, Joehanes, R, Murabito, J M, Kiel, D P, Tsai, P-C, Yet, I, Bell, J T, Mangino, M, Tanaka, T, Mcrae, A F, Marioni, R E, Visscher, P M, Wray, N R, Deary, I J, Levine, M E, Quach, A, Assimes, T L, Tsao, P S, Absher, D, Stewart, J D, Li, Y, Reiner, A P, Hou, L, Baccarelli, A A, Whitsel, E A, Aviv, A, Cardona, A, Day, F R, Wareham, N J, Perry, J R B, Ong, K K, Raj, K, Lunetta, K L & Horvath, S 2018, ' GWAS of epigenetic aging rates in blood reveals a critical role for TERT ', Nature Communications, vol. 9, no. 1, 387 . https://doi.org/10.1038/s41467-017-02697-5
Publication Year :
2017

Abstract

DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA. Variants associated with longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase gene (TERT) paradoxically confer higher IEAA (P<br />Epigenetic clocks based on DNA methylation levels are estimators of chronological age. Here, the authors perform a GWAS of epigenetic aging rates in blood and find SNP variants in the TERT locus associated with increased intrinsic epigenetic age are also associated with longer telomeres.

Details

ISSN :
20411723
Volume :
9
Issue :
1
Database :
OpenAIRE
Journal :
Nature communications
Accession number :
edsair.doi.dedup.....56840d378bc73cbae5c2eefbadddec46