dc.contributor.author | Huan, Tianxiao | |
dc.contributor.author | Nguyen, Steve | |
dc.contributor.author | Colicino, Elena | |
dc.contributor.author | Ochoa-Rosales, Carolina | |
dc.contributor.author | Hill, W David | |
dc.contributor.author | Brody, Jennifer A | |
dc.contributor.author | Soerensen, Mette | |
dc.contributor.author | Zhang, Yan | |
dc.contributor.author | Baldassari, Antoine | |
dc.contributor.author | Elhadad, Mohamed Ahmed | |
dc.contributor.author | Toshiko, Tanaka | |
dc.contributor.author | Zheng, Yinan | |
dc.contributor.author | Domingo-Relloso, Arce | |
dc.contributor.author | Lee, Dong Heon | |
dc.contributor.author | Ma, Jiantao | |
dc.contributor.author | Yao, Chen | |
dc.contributor.author | Liu, Chunyu | |
dc.contributor.author | Hwang, Shih-Jen | |
dc.contributor.author | Joehanes, Roby | |
dc.contributor.author | Fornage, Myriam | |
dc.contributor.author | Bressler, Jan | |
dc.contributor.author | van Meurs, Joyce B J | |
dc.contributor.author | Debrabant, Birgit | |
dc.contributor.author | Mengel-From, Jonas | |
dc.contributor.author | Hjelmborg, Jacob | |
dc.contributor.author | Christensen, Kaare | |
dc.contributor.author | Vokonas, Pantel | |
dc.contributor.author | Schwartz, Joel | |
dc.contributor.author | Gahrib, Sina A | |
dc.contributor.author | Sotoodehnia, Nona | |
dc.contributor.author | Sitlani, Colleen M | |
dc.contributor.author | Kunze, Sonja | |
dc.contributor.author | Gieger, Christian | |
dc.contributor.author | Peters, Annette | |
dc.contributor.author | Waldenberger, Melanie | |
dc.contributor.author | Deary, Ian J | |
dc.contributor.author | Ferrucci, Luigi | |
dc.contributor.author | Qu, Yishu | |
dc.contributor.author | Greenland, Philip | |
dc.contributor.author | Lloyd-Jones, Donald M | |
dc.contributor.author | Hou, Lifang | |
dc.contributor.author | Bandinelli, Stefania | |
dc.contributor.author | Voortman, Trudy | |
dc.contributor.author | Hermann, Brenner | |
dc.contributor.author | Baccarelli, Andrea | |
dc.contributor.author | Whitsel, Eric | |
dc.contributor.author | Pankow, James S | |
dc.contributor.author | Levy, Daniel | |
dc.contributor.author | Ochoa‐Rosales, Carolina | |
dc.contributor.author | Hill, W. David | |
dc.contributor.author | Brody, Jennifer A. | |
dc.contributor.author | Domingo‐Relloso, Arce | |
dc.contributor.author | Hwang, Shih‐Jen | |
dc.contributor.author | van Meurs, Joyce B.J. | |
dc.contributor.author | Mengel‐From, Jonas | |
dc.contributor.author | Gahrib, Sina A. | |
dc.contributor.author | Sitlani, Colleen M. | |
dc.contributor.author | Deary, Ian J. | |
dc.contributor.author | Lloyd‐Jones, Donald M. | |
dc.contributor.author | Pankow, James S. | |
dc.contributor.author | Meurs, Joyce B.J. | |
dc.date.accessioned | 2022-11-16T11:20:06Z | |
dc.date.available | 2022-11-16T11:20:06Z | |
dc.date.issued | 2022-06 | |
dc.identifier.citation | Aging Cell. 2022 Jun;21(6):e13608. | es_ES |
dc.identifier.issn | 1474-9718 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/15165 | |
dc.description.abstract | DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10-7 , of which 41 (EA) and 16 (AA) were also associated with CVD death, and 15 (EA) and 9 (AA) with cancer death. We built DNAm-based prediction models for all-cause mortality that predicted mortality risk after adjusting for clinical risk factors. The mortality prediction model trained by integrating DNAm with clinical risk factors showed an improvement in prediction of cancer death with 5% increase in the C-index in a replication cohort, compared with the model including clinical risk factors alone. Mendelian randomization identified 15 putatively causal CpGs in relation to longevity, CVD, or cancer risk. For example, cg06885782 (in KCNQ4) was positively associated with risk for prostate cancer (Beta = 1.2, PMR = 4.1 × 10-4 ) and negatively associated with longevity (Beta = -1.9, PMR = 0.02). Pathway analysis revealed that genes associated with mortality-related CpGs are enriched for immune- and cancer-related pathways. We identified replicable DNAm signatures of mortality and demonstrated the potential utility of CpGs as informative biomarkers for prediction of mortality risk. | es_ES |
dc.description.sponsorship | The Framingham Heart Study is funded by National Institutes of Health contract N01-HC-25195 and HHSN268201500001I. The laboratory work for this investigation was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. The analytical component of this project was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, and the Center for Information Technology, National Institutes of Health, Bethesda, MD. The Cardiovascular Health Study is supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, U01HL130114, K08HL116640, R01HL087652, R01HL092111, R01HL103612, R01HL105756, R01HL103612, R01HL111089, R01HL116747 and R01HL120393 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA), Merck Foundation/Society of Epidemiologic Research as well as Laughlin Family, Alpha Phi Foundation, and Locke Charitable Foundation. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant R01HL105756. The DTR study was supported by The Danish Council for Independent Research-Medical Sciences (DFF-6110-00016), the European Union's Seventh Framework Programme (FP7/2007–2011) under grant Agreement No. 259679 and The Danish National Program for Research Infrastructure 2007 (09-063256). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. Work in WHI was NIEHS-supported by R01-ES020836 (EAW; AB; LH). Phenotype collection in the Lothian Birth Cohort 1921 was supported by the UK’s Biotechnology and Biological Sciences Research Council (BBSRC), The Royal Society and The Chief Scientist Office of the Scottish Government. Phenotype collection in the Lothian Birth Cohort 1936 was supported by Age UK (The Disconnected Mind project). Methylation typing was supported by Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. IJD is a member of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), which is supported by funding from the BBSRC, the Medical Research Council (MRC), and the University of Edinburgh as part of the cross-council Lifelong Health and Wellbeing initiative (MR/K026992/1). W.D.H. is supported by a grant from Age UK (Disconnected Mind Project). The VA Normative Aging Study is sponsored by the CSP/ERIC program of the U.S. Department of Veterans Affairs and is a research component of the Massachusetts Veterans Education Research and Information Center (MAVERIC). The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. 75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, and 75N92022D00005. Funding was also supported by 5RC2HL102419 and R01NS087541. The authors thank the staff and participants of the ARIC study for their important contributions. J.M. is supported by a grant from NIH HL135075. W.D.H. is supported by a Career Development Award from the Medical Research Council (MRC) [MR/T030852/1] for the project titled “From genetic sequence to phenotypic consequence: genetic and environmental links between cognitive ability, socioeconomic position, and health.” | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Cancer | es_ES |
dc.subject | Cardiovascular disease | es_ES |
dc.subject | DNA methylation | es_ES |
dc.subject | Machine learning | es_ES |
dc.subject | Mortality | es_ES |
dc.subject.mesh | Cardiovascular Diseases | es_ES |
dc.subject.mesh | Neoplasms | es_ES |
dc.subject.mesh | Biomarkers | es_ES |
dc.subject.mesh | DNA Methylation | es_ES |
dc.subject.mesh | Epigenesis, Genetic | es_ES |
dc.subject.mesh | Epigenomics | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Male | es_ES |
dc.title | Integrative analysis of clinical and epigenetic biomarkers of mortality | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 35546478 | es_ES |
dc.format.volume | 21 | es_ES |
dc.format.number | 6 | es_ES |
dc.format.page | e13608 | es_ES |
dc.identifier.doi | 10.1111/acel.13608 | es_ES |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | es_ES |
dc.contributor.funder | NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos) | es_ES |
dc.contributor.funder | NIH - Center for Information Technology (Estados Unidos) | es_ES |
dc.contributor.funder | NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos) | es_ES |
dc.contributor.funder | NIH - National Institute on Aging (NIA) (Estados Unidos) | es_ES |
dc.contributor.funder | Fundación Merck Salud | es_ES |
dc.contributor.funder | Laughlin Family | es_ES |
dc.contributor.funder | Alpha Phi Foundation | es_ES |
dc.contributor.funder | Locke Charitable Foundation | es_ES |
dc.contributor.funder | National Center for Advancing Translational Sciences (Estados Unidos) | es_ES |
dc.contributor.funder | NIH - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (Estados Unidos) | es_ES |
dc.contributor.funder | Danish Council for Independent Research | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. 7 Programa Marco | es_ES |
dc.contributor.funder | United States Department of Health and Human Services | es_ES |
dc.contributor.funder | NIH - National Institute of Environmental Health Sciences (NIEHS) (Estados Unidos) | es_ES |
dc.contributor.funder | Biotechnology and Biological Sciences Research Council (Reino Unido) | es_ES |
dc.contributor.funder | Royal Society (Reino Unido) | es_ES |
dc.contributor.funder | Scottish Government (Reino Unido) | es_ES |
dc.contributor.funder | Age UK (Reino Unido) | es_ES |
dc.contributor.funder | Centre for Cognitive Ageing and Cognitive Epidemiology (Reino Unido) | es_ES |
dc.contributor.funder | Wellcome Trust | es_ES |
dc.contributor.funder | University of Edinburgh (Reino Unido) | es_ES |
dc.contributor.funder | University of Queensland (Australia) | es_ES |
dc.contributor.funder | Medical Research Council (Reino Unido) | es_ES |
dc.contributor.funder | United States Department of Veterans Affairs | es_ES |
dc.contributor.funder | Massachusetts Veterans Education Research and Information Center (MAVERIC) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1474-9726 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1111/acel.13608 | es_ES |
dc.identifier.journal | Aging cell | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Epidemiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/259679/EU | es_ES |
dc.rights.accessRights | open access | es_ES |