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Blood DNA methylation sites predict death risk in a longitudinal study of 12,300 individuals

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Blood DNA methylation sites predict death risk in a longitudinal study of 12,300 individuals. / 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.

In: Aging, Vol. 12, No. 14, 31.07.2020, p. 14092-14124.

Research output: Contribution to journalArticle

Harvard

Colicino, E, Marioni, R, Ward-Caviness, C, Gondalia, R, Guan, W, Chen, B, Tsai, PC, Huan, T, Xu, G, Golareh, A, Schwartz, J, Vokonas, P, Just, A, Starr, JM, McRae, AF, Wray, NR, Visscher, PM, Bressler, J, Zhang, W, Tanaka, T, Moore, AZ, Pilling, LC, Zhang, G, Stewart, JD, Li, Y, Hou, L, Castillo-Fernandez, J, Spector, T, Kiel, DP, Murabito, JM, Liu, C, Mendelson, M, Assimes, T, Absher, D, Tsaho, PS, Lu, AT, Ferrucci, L, Wilson, R, Waldenberger, M, Prokisch, H, Bandinelli, S, Bell, JT, Levy, D, Deary, IJ, Horvath, S, Pankow, J, Peters, A, Whitsel, EA & Baccarelli, A 2020, 'Blood DNA methylation sites predict death risk in a longitudinal study of 12,300 individuals', Aging, vol. 12, no. 14, pp. 14092-14124. https://doi.org/10.18632/aging.103408

APA

Colicino, E., Marioni, R., Ward-Caviness, C., Gondalia, R., Guan, W., Chen, B., Tsai, P. C., Huan, T., Xu, G., Golareh, A., Schwartz, J., Vokonas, P., Just, A., Starr, J. M., McRae, A. F., Wray, N. R., Visscher, P. M., Bressler, J., Zhang, W., ... Baccarelli, A. (2020). Blood DNA methylation sites predict death risk in a longitudinal study of 12,300 individuals. Aging, 12(14), 14092-14124. https://doi.org/10.18632/aging.103408

Vancouver

Colicino E, Marioni R, Ward-Caviness C, Gondalia R, Guan W, Chen B et al. Blood DNA methylation sites predict death risk in a longitudinal study of 12,300 individuals. Aging. 2020 Jul 31;12(14):14092-14124. https://doi.org/10.18632/aging.103408

Author

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. / Blood DNA methylation sites predict death risk in a longitudinal study of 12,300 individuals. In: Aging. 2020 ; Vol. 12, No. 14. pp. 14092-14124.

Bibtex Download

@article{d0e3d8a5b5aa48e48e8e776a592d0f19,
title = "Blood DNA methylation sites predict death risk in a longitudinal study of 12,300 individuals",
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 < 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 = "Aging, All-cause mortality, DNA methylation, 450K, Epigenome-wide association studies",
author = "Elena Colicino and Riccardo Marioni and Cavin Ward-Caviness and Rahul Gondalia and Weihua Guan and Brian Chen and Tsai, {Pei Chien} and Tianxiao Huan and Gao Xu and Agha Golareh and Joel Schwartz and Pantel Vokonas and Allan Just and Starr, {John M.} and McRae, {Allan F.} and Wray, {Naomi R.} and Visscher, {Peter M.} and Jan Bressler and Wen Zhang and Toshiko Tanaka and Moore, {Ann Zenobia} and Pilling, {Luke C.} and Guosheng Zhang and Stewart, {James D.} and Yun Li and Lifang Hou and Juan Castillo-Fernandez and Tim Spector and Kiel, {Douglas P.} and Murabito, {Joanne M.} and Chunyu Liu and Mike Mendelson and Tim Assimes and Devin Absher and Tsaho, {Phil S.} and Lu, {Ake T.} and Luigi Ferrucci and Rory Wilson and Melanie Waldenberger and Holger Prokisch and Stefania Bandinelli and Bell, {Jordana T.} and Daniel Levy and Deary, {Ian J.} and Steve Horvath and Jim Pankow and Annette Peters and Whitsel, {Eric A.} and Andrea Baccarelli",
year = "2020",
month = jul,
day = "31",
doi = "10.18632/aging.103408",
language = "English",
volume = "12",
pages = "14092--14124",
journal = "Aging",
issn = "1945-4589",
publisher = "Springer International Publishing AG",
number = "14",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Blood DNA methylation sites predict death risk in a longitudinal study of 12,300 individuals

AU - Colicino, Elena

AU - Marioni, Riccardo

AU - Ward-Caviness, Cavin

AU - Gondalia, Rahul

AU - Guan, Weihua

AU - Chen, Brian

AU - Tsai, Pei Chien

AU - Huan, Tianxiao

AU - Xu, Gao

AU - Golareh, Agha

AU - Schwartz, Joel

AU - Vokonas, Pantel

AU - Just, Allan

AU - Starr, John M.

AU - McRae, Allan F.

AU - Wray, Naomi R.

AU - Visscher, Peter M.

AU - Bressler, Jan

AU - Zhang, Wen

AU - Tanaka, Toshiko

AU - Moore, Ann Zenobia

AU - Pilling, Luke C.

AU - Zhang, Guosheng

AU - Stewart, James D.

AU - Li, Yun

AU - Hou, Lifang

AU - Castillo-Fernandez, Juan

AU - Spector, Tim

AU - Kiel, Douglas P.

AU - Murabito, Joanne M.

AU - Liu, Chunyu

AU - Mendelson, Mike

AU - Assimes, Tim

AU - Absher, Devin

AU - Tsaho, Phil S.

AU - Lu, Ake T.

AU - Ferrucci, Luigi

AU - Wilson, Rory

AU - Waldenberger, Melanie

AU - Prokisch, Holger

AU - Bandinelli, Stefania

AU - Bell, Jordana T.

AU - Levy, Daniel

AU - Deary, Ian J.

AU - Horvath, Steve

AU - Pankow, Jim

AU - Peters, Annette

AU - Whitsel, Eric A.

AU - Baccarelli, Andrea

PY - 2020/7/31

Y1 - 2020/7/31

N2 - 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 < 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.

AB - 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 < 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.

KW - Aging

KW - All-cause mortality

KW - DNA methylation, 450K

KW - Epigenome-wide association studies

UR - http://www.scopus.com/inward/record.url?scp=85088842670&partnerID=8YFLogxK

U2 - 10.18632/aging.103408

DO - 10.18632/aging.103408

M3 - Article

AN - SCOPUS:85088842670

VL - 12

SP - 14092

EP - 14124

JO - Aging

JF - Aging

SN - 1945-4589

IS - 14

ER -

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