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

Ake T. Lu, Luting Xue, Elias L. Salfati, Brian H. Chen, Luigi Ferrucci, Daniel Levy, Roby Joehanes, Joanne M. Murabito, Douglas P. Kiel, Pei-Chien Tsai, Idil Yet, Jordana T. Bell, Massimo Mangino, Toshiko Tanaka, Allan F. McRae, Riccardo E. Marioni, Peter M. Visscher, Naomi R. Wray, Ian J. Deary, Morgan E. Levine, Austin Quach, Themistocles Assimes, Philip S. Tsao, Devin Absher, James D. Stewart, Yun Li, Alex P. Reiner, Lifang Hou, Andrea A. Baccarelli, Eric A. Whitsel, Abraham Aviv, Alexia Cardona, Felix R. Day, Nicholas J. Wareham, John R. B. Perry, Ken K. Ong, Kenneth Raj, Kathryn L. Lunetta and Steve Horvath ()
Additional contact information
Ake T. Lu: University of California, Los Angeles
Luting Xue: Boston University School of Public Health
Elias L. Salfati: Stanford University School of Medicine
Brian H. Chen: National Institute on Aging, National Institutes of Health
Luigi Ferrucci: National Institute on Aging, National Institutes of Health
Daniel Levy: National Heart, Lung and Blood Institute
Roby Joehanes: National Heart, Lung and Blood Institute
Joanne M. Murabito: Boston University School of Medicine
Douglas P. Kiel: Harvard Medical School
Pei-Chien Tsai: Kings College London
Idil Yet: Kings College London
Jordana T. Bell: Kings College London
Massimo Mangino: Kings College London
Toshiko Tanaka: National Institute on Aging, National Institutes of Health
Allan F. McRae: The University of Queensland
Riccardo E. Marioni: The University of Queensland
Peter M. Visscher: The University of Queensland
Naomi R. Wray: The University of Queensland
Ian J. Deary: University of Edinburgh
Morgan E. Levine: University of California, Los Angeles
Austin Quach: University of California, Los Angeles
Themistocles Assimes: Stanford University School of Medicine
Philip S. Tsao: Stanford University School of Medicine
Devin Absher: HudsonAlpha Institute for Biotechnology
James D. Stewart: University of North Carolina
Yun Li: University of North Carolina
Alex P. Reiner: Fred Hutchinson Cancer Research Center Box 358080, WHI Clinical Coordinating Ctr/Public Health Sciences M3-A4
Lifang Hou: Northwestern University Chicago
Andrea A. Baccarelli: Columbia University Mailman School of Public Health
Eric A. Whitsel: University of North Carolina
Abraham Aviv: University of Medicine and Dentistry, New Jersey Medical School
Alexia Cardona: University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus
Felix R. Day: University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus
Nicholas J. Wareham: University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus
John R. B. Perry: University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus
Ken K. Ong: University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus
Kenneth Raj: Chemical and Environmental Hazards, Public Health England, Chilton
Kathryn L. Lunetta: Boston University School of Public Health
Steve Horvath: University of California, Los Angeles

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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

Date: 2018
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DOI: 10.1038/s41467-017-02697-5

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