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Record W3087330846 · doi:10.1101/2020.09.01.20180406

Genomic and phenomic insights from an atlas of genetic effects on DNA methylation

2020· preprint· en· W3087330846 on OpenAlexaff
Josine L. Min, Gibran Hemani, Eilís Hannon, Koen F. Dekkers, Juan Castillo‐Fernandez, René Luijk, Elena Carnero‐Montoro, Daniel J. Lawson, Kimberley Burrows, Matthew Suderman, Andrew D. Bretherick, Tom G. Richardson, Johanna Klughammer, Valentina Iotchkova, Gemma C. Sharp, Ahmad Al Khleifat, Aleksey Shatunov, Alfredo Iacoangeli, Wendy L. McArdle, Karen Ho, Ashish Kumar, Cilla Söderhäll, Carolina Soriano‐Tárraga, Eva Giralt‐Steinhauer, Nabila Kazmi, Dan Mason, Allan F. McRae, David L. Corcoran, Karen Sugden, Silva Kasela, Alexia Cardona, Felix R. Day, Giovanni Cugliari, Clara Viberti, Simonetta Guarrera, Michael C. Lerro, Richa Gupta, Sailalitha Bollepalli, Pooja R. Mandaviya, Yanni Zeng, Toni‐Kim Clarke, Rosie M. Walker, Vanessa Schmoll, Darina Czamara, Carlos Ruiz-Arenas, Faisal I. Rezwan, Riccardo E. Marioni, Tian Lin, Yvonne Awaloff, Marine Germain, Dylan Aïssi, Ramona A.J. Zwamborn, Kristel van Eijk, Annelot M. Dekker, Jenny van Dongen, Jouke‐Jan Hottenga, Gonneke Willemsen, Cheng‐Jian Xu, Guillermo Barturen, Francesc Català‐Moll, Martin Kerick, Carol A. Wang, Phillip E. Melton, Hannah R. Elliott, Jean Shin, Manon Bernard, İdil Yet, Melissa Smart, T.J. Gorrie-Stone, Chris Shaw, Ammar Al‐Chalabi, Susan M. Ring, Göran Pershagen, Erik Melén, Jordi Jiménez-Conde, Jaume Roquer, Debbie A. Lawlor, John Wright, Nicholas G. Martin, Grant W. Montgomery, Terrie E. Moffitt, Richie Poulton, Tõnu Esko, Lili Milani, Andres Metspalu, John R. B. Perry, Ken K. Ong, Nicholas J Wareham, Giuseppe Matullo, Carlotta Sacerdote, Avshalom Caspi, Louise Arseneault, France Gagnon, Miina Ollikainen, Jaakko Kaprio, Janine F. Felix, Fernando Rivadeneira, Henning Tiemeier, Marinus H. van IJzendoorn, André G. Uitterlinden, Vincent W. V. Jaddoe, Chris Haley, Andrew M McIntosh, Kathryn L. Evans, Alison D. Murray, Katri Räikkönen, Jari Lahti, Ellen A. Nøhr, Thorkild I. A. Sørensen, Torben Hansen, Camilla S. Morgen, Elisabeth B. Binder, Susanne Lucae, Juan Ramon Gonzalez, Mariona Bustamante, Jordi Sunyer, John W. Holloway, Wilfried Karmaus, Hongmei Zhang, Ian J. Deary, Naomi R. Wray, John M. Starr, Marian Beekman, P. Eline Slagboom, Pierre‐Emmanuel Morange, David‐Alexandre Trégouët, Jan H. Veldink, Gareth E. Davies, Eco J. C. de Geus, Dorret I. Boomsma, Judith M. Vonk, Bert Brunekreef, Gerard H. Koppelman, Marta E. Alarcón‐Riquelme, Rae‐Chi Huang, Craig E. Pennell, Joyce B. J. van Meurs, M. Arfan Ikram, Alun D. Hughes, Therese Tillin, Nish Chaturvedi, Zdenka Pausová, Tomáš Paus, Timothy D. Spector, Meena Kumari, Leonard C. Schalkwyk, Peter M. Visscher, George Davey Smith, Christoph Bock, Tom R. Gaunt, Jordana T. Bell, Bastiaan T. Heijmans, Jonathan Mill, Caroline L. Relton

Bibliographic record

VenuemedRxiv · 2020
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsHolland Bloorview Kids Rehabilitation HospitalSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersEconomic and Social Research CouncilMedical Research Council
KeywordsdNaMBiologyQuantitative trait locusDNA methylationGeneticsGenetic architectureEvolutionary biologyComputational biologyGeneGene expression

Abstract

fetched live from OpenAlex

Abstract Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTL of which 8.5% comprise long-range ( trans ) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We reveal that the genetic architecture of DNAm levels is highly polygenic and DNAm exhibits signatures of negative and positive natural selection. Using shared genetic control between distal DNAm sites we construct networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic factors are associated with both blood DNAm levels and complex diseases but in most cases these associations do not reflect causal relationships from DNAm to trait or vice versa indicating a more complex genotype-phenotype map than has previously been hypothesised.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.320
Threshold uncertainty score1.000

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 head0.014
GPT teacher head0.257
Teacher spread0.242 · 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 designBench or experimental
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

Citations36
Published2020
Admission routes1
Has abstractyes

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