@article {27247,
	title = {Blood DNA methylation sites predict death risk in a longitudinal study of 12, 300 individuals},
	journal = {Aging (Albany NY)},
	volume = {12},
	year = {2020},
	note = {Colicino, Elena Marioni, Riccardo Ward-Caviness, Cavin Gondalia, Rahul Guan, Weihua Chen, Brian Tsai, Pei-Chien Huan, Tianxiao Xu, Gao Golareh, Agha Schwartz, Joel Vokonas, Pantel Just, Allan Starr, John M McRae, Allan F Wray, Naomi R Visscher, Peter M Bressler, Jan Zhang, Wen Tanaka, Toshiko Moore, Ann Zenobia Pilling, Luke C Zhang, Guosheng Stewart, James D Li, Yun Hou, Lifang Castillo-Fernandez, Juan Spector, Tim Kiel, Douglas P Murabito, Joanne M Liu, Chunyu Mendelson, Mike Assimes, Tim Absher, Devin Tsaho, Phil S Lu, Ake T Ferrucci, Luigi Wilson, Rory Waldenberger, Melanie Prokisch, Holger Bandinelli, Stefania Bell, Jordana T Levy, Daniel Deary, Ian J Horvath, Steve Pankow, Jim Peters, Annette Whitsel, Eric A Baccarelli, Andrea eng Aging (Albany NY). 2020 Jul 22;12. pii: 103408. doi: 10.18632/aging.103408.},
	type = {Journal Article},
	abstract = {DNA methylation has fundamental roles in gene programming and aging that may help predict mortality. However, no large-scale study has investigated whether site-specific DNA methylation predicts all-cause mortality. We used the Illumina-HumanMethylation450-BeadChip to identify blood DNA methylation sites associated with all-cause mortality for 12, 300 participants in 12 Cohorts of the Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium. Over an average 10-year follow-up, there were 2,561 deaths across the cohorts. Nine sites mapping to three intergenic and six gene-specific regions were associated with mortality (P \&lt; 9.3x10(-7)) independently of age and other mortality predictors. Six sites (cg14866069, cg23666362, cg20045320, cg07839457, cg07677157, cg09615688)-mapping respectively to BMPR1B, MIR1973, IFITM3, NLRC5, and two intergenic regions-were associated with reduced mortality risk. The remaining three sites (cg17086398, cg12619262, cg18424841)-mapping respectively to SERINC2, CHST12, and an intergenic region-were associated with increased mortality risk. DNA methylation at each site predicted 5\%-15\% of all deaths. We also assessed the causal association of those sites to age-related chronic diseases by using Mendelian randomization, identifying weak causal relationship between cg18424841 and cg09615688 with coronary heart disease. Of the nine sites, three (cg20045320, cg07839457, cg07677157) were associated with lower incidence of heart disease risk and two (cg20045320, cg07839457) with smoking and inflammation in prior CHARGE analyses. Methylation of cg20045320, cg07839457, and cg17086398 was associated with decreased expression of nearby genes (IFITM3, IRF, NLRC5, MT1, MT2, MARCKSL1) linked to immune responses and cardiometabolic diseases. These sites may serve as useful clinical tools for mortality risk assessment and preventative care.},
	keywords = {450k DNA methylation aging all-cause mortality epigenome-wide association studies},
	issn = {1945-4589 (Electronic) 1945-4589 (Linking)},
	doi = {10.18632/aging.103408},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/32697766},
	author = {Colicino, E. and Marioni, R. and Ward-Caviness, C. and Gondalia, R. and Guan, W. and B. Chen and Tsai, P. C. and Huan, T. and Xu, G. and Golareh, A. and Schwartz, J. and Vokonas, P. and Just, A. and Starr, J. M. and McRae, A. F. and Wray, N. R. and Visscher, P. M. and Bressler, J. and W. Zhang and Tanaka, T. and Moore, A. Z. and Pilling, L. C. and G. Zhang and Stewart, J. D. and Y. Li and Hou, L. and Castillo-Fernandez, J. and Spector, T. and Kiel, D. P. and Murabito, J. M. and C. Liu and Mendelson, M. and Assimes, T. and Absher, D. and Tsaho, P. S. and Lu, A. T. and Ferrucci, L. and Wilson, R. and Waldenberger, M. and Prokisch, H. and Bandinelli, S. and Bell, J. T. and Levy, D. and Deary, I. J. and Horvath, S. and Pankow, J. and Peters, A. and Whitsel, E. A. and Baccarelli, A.}
}
