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Record W2940767756 · doi:10.1038/s41467-019-09671-3

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

2019· review· en· W2940767756 on OpenAlexaff
Leanne K. Küpers, Claire Monnereau, Gemma C. Sharp, Paul Yousefi, Lucas A. Salas, Akram Ghantous, Christian M. Page, Sarah E. Reese, Allen J. Wilcox, Darina Czamara, Anne P. Starling, Alexei Novoloaca, Samantha Lent, Ritu Roy, Cathrine Hoyo, Carrie V. Breton, Catherine Allard, Allan C. Just, Kelly M. Bakulski, John W. Holloway, Todd M. Everson, Cheng‐Jian Xu, Rae‐Chi Huang, Diana A. van der Plaat, Matthias Wielscher, Simon Kebede Merid, Vilhelmina Ullemar, Faisal I. Rezwan, Jari Lahti, Jenny van Dongen, Sabine A. S. Langie, Tom G. Richardson, Maria C. Magnus, Ellen A. Nøhr, Zongli Xu, Liesbeth Duijts, Shanshan Zhao, Weimin Zhang, Michelle Plusquin, Dawn L. DeMeo, Olivia Solomon, Joosje H. Heimovaara, Dereje D. Jima, Lu Gao, Mariona Bustamante, Patrice Perron, Robert O. Wright, Irva Hertz‐Picciotto, Hongmei Zhang, Margaret R. Karagas, Ulrike Gehring, Carmen J. Marsit, Lawrence J. Beilin, Judith M. Vonk, Marjo‐Riitta Järvelin, Anna Bergström, Anne K. Örtqvist, Susan Ewart, Pia Villa, Sophie E. Moore, Gonneke Willemsen, Arnout Standaert, Siri E. Håberg, Thorkild I. A. Sørensen, Jack A. Taylor, Katri Räikkönen, Ivana V. Yang, Katerina Kechris, Tim S. Nawrot, Matt J. Silver, Yun Yun Gong, Lorenzo Richiardi, Manolis Kogevinas, Augusto A. Litonjua, Brenda Eskenazi, Karen Huen, Hamdi Mbarek, Rachel L. Maguire, Terence Dwyer, Martine Vrijheid, Luigi Bouchard, Andrea Baccarelli, Lisa Croen, Wilfried Karmaus, Denise Anderson, Maaike de Vries, Sylvain Sebért, Juha Kere, Robert Karlsson, Syed Hasan Arshad, Esa Hämäläinen, Michael N. Routledge, Dorret I. Boomsma, Andrew P. Feinberg, Craig J. Newschaffer, Eva Govarts, Matthieu Moisse, M. Daniele Fallin, Erik Melén, Andrew M. Prentice, Eero Kajantie, Catarina Almqvist, Emily Oken, Dana Dabelea, H. Marike Boezen, Phillip E. Melton, Rosalind J. Wright, Gerard H. Koppelman, Letizia Trevisi, Marie‐France Hivert, Jordi Sunyer, Monica Cheng Munthe‐Kaas, Susan K. Murphy, Eva Corpeleijn, Joseph L. Wiemels, Nina Holland, Zdenko Herceg, Elisabeth B. Binder, George Davey Smith, Vincent W. V. Jaddoe, Rolv T. Lie, Wenche Nystad, Stephanie J. London, Debbie A. Lawlor, Caroline L. Relton, Harold Snieder, Janine F. Felix

Bibliographic record

VenueNature Communications · 2019
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsCégep de ChicoutimiUniversité de SherbrookeCentre Hospitalier Universitaire de Sherbrooke
FundersNational Institute on Minority Health and Health DisparitiesMedical Research CouncilNational Institute of Allergy and Infectious DiseasesBiotechnology and Biological Sciences Research CouncilNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNational Institutes of HealthNational Institute of Environmental Health SciencesNational Institute for Health and Care ResearchNovo Nordisk FondenEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEconomic and Social Research CouncilWorld Health Organization
KeywordsEpigenomeDNA methylationGeneticsEpigeneticsBiologyAssociation (psychology)MethylationMedicineComputational biologyDNABioinformaticsGenePsychologyGene expression

Abstract

fetched live from OpenAlex

Abstract Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni < 1.06 x 10 −7 ). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.436
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.152
GPT teacher head0.396
Teacher spread0.245 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designMeta-analysis
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations263
Published2019
Admission routes1
Has abstractyes

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