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dc.contributor.author | Christiansen, C | |
dc.contributor.author | Castillo-Fernandez, J E | |
dc.contributor.author | Domingo-Relloso, Arce | |
dc.contributor.author | Zhao, W | |
dc.contributor.author | El-Sayed Moustafa, J S | |
dc.contributor.author | Tsai, P-C | |
dc.contributor.author | Maddock, J | |
dc.contributor.author | Haack, K | |
dc.contributor.author | Cole, S A | |
dc.contributor.author | Kardia, S L R | |
dc.contributor.author | Molokhia, M | |
dc.contributor.author | Suderman, M | |
dc.contributor.author | Power, C | |
dc.contributor.author | Relton, C | |
dc.contributor.author | Wong, A | |
dc.contributor.author | Kuh, D | |
dc.contributor.author | Goodman, A | |
dc.contributor.author | Small, K S | |
dc.contributor.author | Smith, J A | |
dc.contributor.author | Tellez-Plaza, Maria | |
dc.contributor.author | Navas-Acien, Ana | |
dc.contributor.author | Ploubidis, G B | |
dc.contributor.author | Hardy, R | |
dc.contributor.author | Bell, J T | |
dc.date.accessioned | 2021-03-26T12:32:25Z | |
dc.date.available | 2021-03-26T12:32:25Z | |
dc.date.issued | 2021-02-16 | |
dc.identifier.citation | Clin Epigenetics. 2021 Feb 16;13(1):36. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/12447 | |
dc.description.abstract | Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk. | es_ES |
dc.description.sponsorship | This study was supported by the Economic and Social Research Council (ESRC, Grant Number ES/N000404/1 to J.T.B). Data governance for access to UK birth cohort data was provided by the METADAC data access committee, funded by ESRC, Wellcome and MRC (2015–2018: Grant Number MR/N01104X/1 2018–2020: Grant Number ES/S008349/1). This work made use of data and samples generated by the 1958 Birth Cohort (NCDS), which is managed by the Centre for Longitudinal Studies at the UCL Institute of Education, funded by the ESRC (Grant Number ES/M001660/1); blood sample collection was funded by MRC (Grant G0000934). Access to these resources was enabled via the Wellcome Trust and MRC: 58FORWARDS Grant (108439/Z/15/Z). Before 2015 biomedical resources were maintained under the Wellcome Trust and Medical Research Council 58READIE Project (Grant Numbers WT095219MA and G1001799). Work undertaken at Great Ormond Street Hospital/University College London, Institute of Child Health, is in part supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The UK Medical Research Council also provided core funding for the MRC National Survey of Health and Development (Grant MC_UU_00019/1). The TwinsUK study is supported by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007–2013); the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility. The SHS study received support from the National Heart, Lung, and Blood Institute (NHLBI) of the USA (under contract numbers 75N92019D00027, 75N92019D00028, 75N92019D00029 and 75N92019D00030) and previous Grants (R01HL090863, R01HL109315, R01HL109301, R01HL109284, R01HL109282 and R01HL109319 and Cooperative Agreements: U01HL41642, U01HL41652, U01HL41654, U01HL65520 and U01HL65521), from the National Institutes of Health Sciences of the USA (R01ES021367, R01ES025216, P42ES010349, P30ES009089) and from “la Caixa” Foundation (ID 100010434) (fellowship code “LCF/BQ/DR19/11740016”). The GENOA study received funding from U01HL054457, RC1HL100185, R01HL119443, R01HL133221, R01HL141292. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | BioMed Central (BMC) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | DNA methylation | es_ES |
dc.subject | Environment | es_ES |
dc.subject | Epigenetics | es_ES |
dc.subject | Lifestyle | es_ES |
dc.subject | SLAMF7 | es_ES |
dc.subject | Smoking | es_ES |
dc.title | Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 33593402 | es_ES |
dc.format.volume | 13 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 36 | es_ES |
dc.identifier.doi | 10.1186/s13148-021-01018-4 | es_ES |
dc.contributor.funder | Economic and Social Research Council (Reino Unido) | |
dc.contributor.funder | Wellcome Trust | |
dc.contributor.funder | Medical Research Council (Reino Unido) | |
dc.contributor.funder | NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos) | |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | |
dc.contributor.funder | Fundación La Caixa | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1868-7083 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1186/s13148-021-01018-4 | es_ES |
dc.identifier.journal | Clinical epigenetics | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Epidemiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |