@article{4042fef2125a4957b911982fab9a271e,
title = "Environmentally sensitive hotspots in the methylome of the early human embryo",
abstract = "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 three datasets covering 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-associated 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 {\textquoteleft}hotspots{\textquoteright} providing a record of environmental influence at periconception constitute a valuable resource for investigating epigenetic mechanisms linking early exposures to lifelong health and disease.",
author = "Silver, {Matt J.} and Ayden Saffari and Kessler, {Noah J.} and Chandak, {Giriraj R.} and Fall, {Caroline H.D.} and Prachand Issarapu and Akshay Dedaniya and Modupeh Betts and Moore, {Sophie E.} and Routledge, {Michael N.} and Zdenko Herceg and Cyrille Cuenin and Maria Derakhshan and James, {Philip T.} and David Monk and Prentice, {Andrew M.}",
note = "Funding Information: The Gambian ENID trial was jointly funded by the UK Medical Research Council (MRC) and the Department for International Development (DFID) under the MRC/DFID Concordat agreement (MRC Program MC-A760-5QX00). Methylation analysis of ENID samples was supported by the Bill & Melinda Gates Foundation (grant no: OPP1 066947). The Gambian EMPHASIS study is jointly funded by MRC, DFID and the Department of Biotechnology, Ministry of Science and Technology, India under the Newton Fund initiative (MRC grant no.: MR/N006208/1 and DBT grant no.: BT/IN/DBT-MRC/DFID/24/GRC/2015?16). Further support for this analysis was provided by MRC Grant MR/M01424X/1. We acknowledge the work of the full EMPHASIS Study Group (www.emphasisstudy.org) in acquiring this data. Publisher Copyright: {\textcopyright} 2022, eLife Sciences Publications Ltd. All rights reserved.",
year = "2022",
month = feb,
doi = "10.7554/ELIFE.72031",
language = "English",
volume = "11",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications, Ltd",
}