Phenome-wide analyses identify an association between the parent-of-origin effects dependent methylome and the rate of aging in humans
dc.contributor.author | Gao, C | |
dc.contributor.author | Amador, C | |
dc.contributor.author | Walker, RM | |
dc.contributor.author | Campbell, A | |
dc.contributor.author | Madden, RA | |
dc.contributor.author | Adams, MJ | |
dc.contributor.author | Bai, X | |
dc.contributor.author | Liu, Y | |
dc.contributor.author | Li, M | |
dc.contributor.author | Hayward, C | |
dc.contributor.author | Porteous, DJ | |
dc.contributor.author | Shen, X | |
dc.contributor.author | Evans, KL | |
dc.contributor.author | Haley, CS | |
dc.contributor.author | McIntosh, AM | |
dc.contributor.author | Navarro, P | |
dc.contributor.author | Zeng, Y | |
dc.date.accessioned | 2023-05-17T10:43:36Z | |
dc.date.issued | 2023-05-15 | |
dc.date.updated | 2023-05-17T10:09:37Z | |
dc.description.abstract | Background: The variation in the rate at which humans age may be rooted in early events acting through the genomic regions that are influenced by such events and subsequently are related to health phenotypes in later life. The parent-of-origin-effect (POE)-regulated methylome includes regions enriched for genetically controlled imprinting effects (the typical type of POE) and regions influenced by environmental effects associated with parents (the atypical POE). This part of the methylome is heavily influenced by early events, making it a potential route connecting early exposures, the epigenome, and aging. We aim to test the association of POE-CpGs with early and later exposures and subsequently with health-related phenotypes and adult aging. Results: We perform a phenome-wide association analysis for the POE-influenced methylome using GS:SFHS (Ndiscovery = 5087, Nreplication = 4450). We identify and replicate 92 POE-CpG-phenotype associations. Most of the associations are contributed by the POE-CpGs belonging to the atypical class where the most strongly enriched associations are with aging (DNAmTL acceleration), intelligence, and parental (maternal) smoking exposure phenotypes. A proportion of the atypical POE-CpGs form co-methylation networks (modules) which are associated with these phenotypes, with one of the aging-associated modules displaying increased within-module methylation connectivity with age. The atypical POE-CpGs also display high levels of methylation heterogeneity, fast information loss with age, and a strong correlation with CpGs contained within epigenetic clocks. Conclusions: These results identify the association between the atypical POE-influenced methylome and aging and provide new evidence for the “early development of origin” hypothesis for aging in humans. | en_GB |
dc.description.sponsorship | National Key Research & Development Program of China | en_GB |
dc.description.sponsorship | General Program of National Natural Science Foundation of China | en_GB |
dc.description.sponsorship | National Institutes of Health (NIH) | en_GB |
dc.description.sponsorship | UK Research and Innovation | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Chief Scientist Office of the Scottish Government Health Directorates | en_GB |
dc.description.sponsorship | Scottish Funding Council | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | NARSAD | en_GB |
dc.description.sponsorship | Royal College of Physicians of Edinburgh | en_GB |
dc.identifier.citation | Vol. 24, article 117 | en_GB |
dc.identifier.doi | https://doi.org/10.1186/s13059-023-02953-6 | |
dc.identifier.grantnumber | 2021ZD0202000 | en_GB |
dc.identifier.grantnumber | 81971270 | en_GB |
dc.identifier.grantnumber | R01MH124873 | en_GB |
dc.identifier.grantnumber | MR/W014386/1 | en_GB |
dc.identifier.grantnumber | U. MC_UU_00007/10 | en_GB |
dc.identifier.grantnumber | MC_PC_U127592696 | en_GB |
dc.identifier.grantnumber | CZD/16/6 | en_GB |
dc.identifier.grantnumber | HR03006 | en_GB |
dc.identifier.grantnumber | 104036/Z/14/Z | en_GB |
dc.identifier.grantnumber | 220857/Z/20/Z | en_GB |
dc.identifier.grantnumber | 104036/Z/14/Z | en_GB |
dc.identifier.grantnumber | 27404 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/133161 | |
dc.identifier | ORCID: 0000-0002-1060-4479 (Walker, Rosie M) | |
dc.language.iso | en | en_GB |
dc.publisher | BMC | en_GB |
dc.relation.url | https://zenodo.org/record/7807379 | en_GB |
dc.relation.url | https://datashare.ed.ac.uk/handle/10283/2988 | en_GB |
dc.rights | © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publi cdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | en_GB |
dc.subject | Atypical parent-of-origin effect | en_GB |
dc.subject | Aging | en_GB |
dc.subject | DNAmTL acceleration | en_GB |
dc.subject | Maternal smoking exposure | en_GB |
dc.subject | Lifestyle | en_GB |
dc.subject | Intelligence | en_GB |
dc.title | Phenome-wide analyses identify an association between the parent-of-origin effects dependent methylome and the rate of aging in humans | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-05-17T10:43:36Z | |
exeter.article-number | 117 | |
dc.description | This is the final version. Available on open access from BMC via the DOI in this record. | en_GB |
dc.description | Availability of data and materials: Summary statistics supporting the conclusions of this article are included within the article and its additional files (Additional file 2: Table S1-S20). The full summary statistics for the association analyses at the single CpG and modular level are available at the following repository link: https://zenodo.org/record/7807379 [80]. The data dictionary for GS:SFHS is available at the URL: https://datashare.ed.ac.uk/handle/10283/2988 [81]. According to the terms of consent, access to DNA methylation and phenotype data in GS:SFHS needs to be approved by the GS Access Committee (https://www.ed.ac.uk/generation-scotland/for-researchers/access, mailto: access@generationscotland.org). The managed access process ensures that approval is granted only to research which comes under the terms of participant consent which does not allow making participant information publicly available. | en_GB |
dc.identifier.eissn | 1474-760X | |
dc.identifier.eissn | 1465-6906 | |
dc.identifier.journal | Genome Biology | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-04-26 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2023-05-15 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-05-17T10:35:08Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2023-05-17T10:43:37Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2023-05-15 |
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cdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.