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Record W2950541136 · doi:10.1038/s41467-019-10461-0

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

2019· article· en· W2950541136 on OpenAlexaff
Darina Czamara, Gökçen Eraslan, Christian M. Page, Jari Lahti, Marius Lahti‐Pulkkinen, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Pia Villa, Rebecca M. Reynolds, Wenche Nystad, Siri E. Håberg, Stephanie J. London, Kieran J. O’Donnell, Elika Garg, Michael J. Meaney, Sonja Entringer, Pathik D. Wadhwa, Claudia Buß, Meaghan J. Jones, David Lin, Julie L. MacIsaac, Michael S. Kobor, Nastassja Koen, Heather J. Zar, Karestan C. Koenen, Shareefa Dalvie, Dan J. Stein, Ivan Kondofersky, Nikola S. Müller, Fabian J. Theis, Naomi R. Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Esben Agerbo, Tracy Air, Till F. M. Andlauer, Silviu‐Alin Bacanu, Marie Bækvad‐Hansen, Aartjan T.F. Beekman, Tim B. Bigdeli, Douglas Blackwood, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg‐Grauholm, Na Cai, Enrique Castelao, Jane Christensen, Toni‐Kim Clarke, Jonathan R. I. Coleman, Lucía Colodro‐Conde, Baptiste Couvy‐Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Neşe Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott‐Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Andreas J. Forstner, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas Folkmann Hansen, Stefan Herms, Ian B. Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke‐Jan Hottenga, David M. Hougaard, Marcus Ising, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick J. McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Högni Óskarsson, Michael J. Owen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Erik Pettersson, Wouter J. Peyrot, Giorgio Pistis, Daniëlle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Margarita Rivera, Saira Saeed Mirza, Robert A. Schoevers, Eva C. Schulte, Ling Shen, Jianxin Shi, Stanley I. Shyn, Engilbert Sigurðsson, Grant Sinnamon, Johannes H. Smit, Daniel J. Smıth, Hreinn Stefánsson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Shantel Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H. Witt, Yang Wu, Hualin Simon Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T. Baune, Dorret I. Boomsma, Sven Cichon, Udo Dannlowski, Eco J. C. de Geus, J. Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J. Grabe, Steven P. Hamilton, Caroline Hayward, Andrew C. Heath, Kenneth S. Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S. Li, Susanne Lucae, Pamela A. F. Madden, Patrik K. E. Magnusson, Nicholas G. Martin, Andrew M. McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller‐Myhsok, Merete Nordentoft, Markus M. Nöthen, Michael O‘Donovan, Sara A. Paciga, Nancy L. Pedersen, Brenda W.J.H. Penninx, Roy H. Perlis, David J. Porteous, James B. Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G. Schulze, Jordan W. Smoller, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M. Weissman, Thomas Werge, Cathryn M. Lewis, Douglas F. Levinson, Gerome Breen, Anders D. Børglum, Patrick F. Sullivan, Katri Räikkönen, Elisabeth B. Binder

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsDalhousie UniversityBC Children's HospitalUniversity of British ColumbiaMcGill UniversityDouglas Mental Health University Institute
FundersNational Institute of Child Health and Human DevelopmentNational Institute of Environmental Health SciencesNational Institute of Mental HealthNational Institutes of HealthUniversity of Cape TownSouth African Medical Research CouncilSigrid Juséliuksen SäätiöMedical Research CouncilSigne ja Ane Gyllenbergin SäätiöJuho Vainion SäätiöFogarty International CenterJane ja Aatos Erkon SäätiöSuomen Lääketieteen SäätiöAcademy of FinlandPäivikki ja Sakari Sohlbergin SäätiöHelse- og OmsorgsdepartementetNovo NordiskBundesministerium für Bildung und ForschungSchool of Medicine, Emory UniversityNovo Nordisk FondenLastentautien TutkimussäätiöNorges ForskningsrådEmory UniversityNational Institute of Neurological Disorders and StrokeBritish Heart FoundationTommy'sWellcome TrustTechnische Universität MünchenHelsingin YliopistoEuropean CommissionEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentBill and Melinda Gates Foundation
KeywordsDNA methylationCord bloodGeneticsEpigeneticsBiologyDNAComputational biologyBioinformaticsGeneGene expression

Abstract

fetched live from OpenAlex

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.631
Threshold uncertainty score0.336

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.010
GPT teacher head0.281
Teacher spread0.271 · 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.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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

Citations151
Published2019
Admission routes1
Has abstractyes

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