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Record W2970001915 · doi:10.1038/s41467-019-11881-8

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

2019· review· en· W2970001915 on OpenAlexfundno aff
Xueping Liu, Dorte Helenius, Line Skotte, Robin N. Beaumont, Matthias Wielscher, Frank Geller, Julius Juodakis, Anubha Mahajan, Jonathan P. Bradfield, Frederick T. J. Lin, Suzanne Vogelezang, Mariona Bustamante, Tarunveer S. Ahluwalia, Niina Pitkänen, Carol A. Wang, Jonas Bačelis, Maria Carolina Borges, Ge Zhang, Bruce Bedell, Robert M. Rossi, Kristin Skogstrand, Shouneng Peng, Wesley K. Thompson, Vivek Appadurai, Debbie A. Lawlor, Ilkka Kalliala, Christine Power, Mark I. McCarthy, Heather A. Boyd, Mary L. Marazita, Håkon Håkonarson, M. Geoffrey Hayes, Denise Scholtens, Fernando Rivadeneira, Vincent W. V. Jaddoe, Rebecca Vinding, Hans Bisgaard, Bridget Knight, Katja Pahkala, Olli T. Raitakari, Øyvind Helgeland, Stefan Johansson, Pål R. Njølstad, João Fadista, Andrew J. Schork, Ron Nudel, Daniel E. Miller, Xiaoting Chen, Matthew T. Weirauch, Preben Bo Mortensen, Anders D. Børglum, Merete Nordentoft, Ole Mors, Ke Hao, Kelli K. Ryckman, David M. Hougaard, Leah C. Kottyan, Craig E. Pennell, Leo‐Pekka Lyytikäinen, Klaus Bønnelykke, Martine Vrijheid, Janine F. Felix, William L. Lowe, Struan F.A. Grant, Elina Hyppönen, Bo Jacobsson, Marjo‐Riitta Järvelin, Louis J. Muglia, Jeffrey C. Murray, Rachel M. Freathy, Thomas Werge, Mads Melbye, Alfonso Buil, Bjarke Feenstra

Bibliographic record

VenueNature Communications · 2019
Typereview
Languageen
FieldMedicine
TopicPrenatal Screening and Diagnostics
Canadian institutionsnot available
FundersNational Institute of Neurological Disorders and StrokeMedical Research CouncilSeventh Framework ProgrammeCincinnati Children’s Research FoundationCollege of Pharmacy, University of MichiganMarch of Dimes Prematurity Research Center Ohio CollaborativeWellcome TrustNatureNational Institute of General Medical SciencesH. Lundbeck A/SHorizon 2020 Framework ProgrammeNovo Nordisk FondenNIHR Great Ormond Street Hospital Biomedical Research CentreSigrid Juséliuksen SäätiöUniversity of TorontoNovo NordiskNational Institute for Health and Care ResearchLundbeckfondenUniversity of MichiganNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Diabetes and Digestive and Kidney DiseasesWellcomeLupus Research AllianceOak FoundationNational Institutes of HealthU.S. Department of Health and Human ServicesMarch of Dimes FoundationCarlsbergfondetEuropean CommissionEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentZonMwBill and Melinda Gates Foundation
KeywordsGeneFetusCytokineBiologyGenomeGestational ageWhole genome sequencingImmunologyGeneticsMedicineBioinformaticsPregnancy

Abstract

fetched live from OpenAlex

Abstract The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0020.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.055
GPT teacher head0.348
Teacher spread0.292 · 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 source (direct Gemma or distilled Codex), not a consensus.

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

Citations103
Published2019
Admission routes1
Has abstractyes

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