{"doi":"10.1101/777508","title":"Environmentally sensitive hotspots in the methylome of the early human embryo","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>In humans, DNA methylation marks inherited from gametes are largely erased following fertilisation, prior to construction of the embryonic methylome. Exploiting a natural experiment of seasonal variation including changes in diet and nutritional status in rural Gambia, we analysed two independent child cohorts and identified 259 CpGs showing consistent associations between season of conception (SoC) and DNA methylation. SoC effects were most apparent in early infancy, with evidence of attenuation by mid-childhood. SoC-associated CpGs were enriched for metastable epialleles, parent-of-origin specific methylation and germline DMRs, supporting a periconceptional environmental influence. Many SoC-sensitive CpGs overlapped enhancers or sites of active transcription in H1 ESCs and fetal tissues. Half were influenced but not determined by measured genetic variants that were independent of SoC. Environmental ‘hotspots’ providing a record of environmental influence at periconception constitute a valuable resource for investigating epigenetic mechanisms linking early exposures to lifelong health and disease.</jats:p>","journal":null,"year":null,"id":636350,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1651507,"name":"Ayden Saffari","orcid":null,"position":1,"is_corresponding":false},{"id":1522003,"name":"Noah J. 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SoC-associated CpGs were enriched for metastable epialleles, parent-of-origin specific methylation and germline DMRs, supporting a periconceptional environmental influence. Many SoC-sensitive CpGs overlapped enhancers or sites of active transcription in H1 ESCs and fetal tissues. Half were influenced but not determined by measured genetic variants that were independent of SoC. Environmental ‘hotspots’ providing a record of environmental influence at periconception constitute a valuable resource for investigating epigenetic mechanisms linking early exposures to lifelong health and disease.</jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":"https://openalex.org/W2973265651","authors":[],"funders":[{"funder_name":"UK Research and Innovation","grant_id":"MR/N006208/1","title":"Epigenetic mechanisms linking maternal pre-conceptional micronutrient supplementation with offspring health in India and The Gambia"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2022,"count":1}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/04/23/777508.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/04/23/777508.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/777508","host_type":"publisher"},{"url":"https://doi.org/10.1101/777508","host_type":"repository"},{"url":"http://hdl.handle.net/2445/184813","host_type":"repository"},{"url":"https://figshare.com/articles/journal_contribution/Environmentally_sensitive_hotspots_in_the_methylome_of_the_early_human_embryo/26824063","host_type":"repository"},{"url":"https://www.repository.cam.ac.uk/handle/1810/334878","host_type":"repository"},{"url":"https://www.repository.cam.ac.uk/handle/1810/335387","host_type":"repository"},{"url":"https://doi.org/10.17863/cam.82315","host_type":"repository"},{"url":"https://doi.org/10.17863/cam.82816","host_type":"repository"},{"url":"https://doi.org/10.7554/elife.72031","host_type":""},{"url":"https://elifesciences.org/download/aHR0cHM6Ly9jZG4uZWxpZmVzY2llbmNlcy5vcmcvYXJ0aWNsZXMvNzIwMzEvZWxpZmUtNzIwMzEtdjEucGRmP2Nhbm9uaWNhbFVyaT1odHRwczovL2VsaWZlc2NpZW5jZXMub3JnL2FydGljbGVzLzcyMDMx/elife-72031-v1.pdf?_hash=EoWgkK9cBLEkWPFPMYWjAGboGeT6GlGFouh%2F1eFKJaw%3D","host_type":""},{"url":"https://dx.doi.org/10.60692/n6x85-k6820","host_type":""},{"url":"https://dx.doi.org/10.17863/cam.82816","host_type":""},{"url":"https://dx.doi.org/10.60692/4ngsm-12657","host_type":""},{"url":"https://dx.doi.org/10.60692/h0wf6-3fj65","host_type":""},{"url":"https://dx.doi.org/10.60692/kc29t-25957","host_type":""},{"url":"https://dx.doi.org/10.17863/cam.82315","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/35188105","host_type":""},{"url":"http://dx.doi.org/10.7554/eLife.72031","host_type":""},{"url":"https://hdl.handle.net/2445/184813","host_type":""},{"url":"https://researchonline.lshtm.ac.uk/id/eprint/4666069/1/elife-72031-v2.pdf","host_type":""},{"url":"https://doaj.org/article/3e0df17bd8c3409aa09b5b63f8a77876","host_type":""},{"url":"https://dx.doi.org/10.1101/777508","host_type":""},{"url":"https://ueaeprints.uea.ac.uk/id/eprint/83980/1/Published_Version.pdf","host_type":""},{"url":"https://eprints.soton.ac.uk/455996/1/Silver_et_al_MANUSCRIPT_IN_WORD_eLife_rev_without_figures.docx","host_type":""},{"url":"https://eprints.soton.ac.uk/455996/2/elife_72031_v2.pdf","host_type":""},{"url":"http://dx.doi.org/10.1101/777508","host_type":""},{"url":"https://doi.org/https://doi.org/10.7554/ELIFE.72031","host_type":""},{"url":"https://doi.org/https://doi.org/10.7554/eLife.72031","host_type":""},{"url":"https://doi.org/https://doi.org/10.7554/eLife.72031.sa0","host_type":""}],"fields_of_study":["Epigenetics and DNA Methylation","Birth, Development, and Health","Prenatal Screening and Diagnostics","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["DNA methylation","Epigenetics","Biology","Germline","Methylation","Differentially methylated regions","Enhancer","Genetics","CpG site","Transcription factor","Gene","Gene expression","Fetal Programming","ADN","global health","Evolutionary biology","Epigenesis, Genetic","Epigenome","Biology (General)","Child","Fetal DNA Analysis","Q","R","Life Sciences","nutrition","Early-Life Conditions","Medicine","epidemiology","parent-of-origin effects","Metilació","Research Article","Human","QH301-705.5","Science","Epigenetic Modifications and Their Functional Implications","610","Environmental Epigenomics","Developmental Origins of Adult Health and Disease","early embryo","Biochemistry, Genetics and Molecular Biology","Health Sciences","genomics","Humans","Molecular Biology","Prenatal Aneuploidy Diagnosis and Screening Techniques","Genetics and Genomics","DNA","metastable epiallele","Embryo, Mammalian","Epidemiology and Global Health","Fertilization","FOS: Biological sciences","Pediatrics, Perinatology and Child Health","CpG Islands","conception"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. 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