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Record W4310537549 · doi:10.1101/2022.11.30.22282929

Genome-wide meta-analysis identifies novel maternal risk variants and enables polygenic prediction of preeclampsia and gestational hypertension

2022· preprint· en· W4310537549 on OpenAlexaff
Michael C. Honigberg, Buu Truong, Raiyan R. Khan, Brenda Xiao, Laxmi Bhatta, Ha My T. Vy, Rafael F. Guerrero, Art Schuermans, Margaret Sunitha Selvaraj, Aniruddh P. Patel, Satoshi Koyama, So Mi Jemma Cho, Shamsudheen Karuthedath Vellarikkal, Mark Trinder, Sarah Urbut, Kathryn J. Gray, Ben Brumpton, Snehal Patil, Sebastian Zöllner, Mariah C. Antopia, Richa Saxena, Girish N. Nadkarni, Ron Do, Qi Yan, Itsik Pe’er, Shefali S. Verma, Rajat M. Gupta, David M. Haas, Hilary C. Martin, David A. van Heel, Triin Laisk, Pradeep Natarajan

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldMedicine
TopicPregnancy and preeclampsia studies
Canadian institutionsUniversity of British Columbia
FundersNational Institute of General Medical SciencesNorwegian Institute of Public HealthFaculty of Medicine and Health, University of SydneyMedical Research CouncilFakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige UniversitetMedical School, University of MichiganNational Institutes of HealthNorges ForskningsrådBelgian American Educational FoundationBarts CharityNational Institute of Child Health and Human DevelopmentNational Institute of Diabetes and Digestive and Kidney DiseasesNorges Teknisk-Naturvitenskapelige UniversitetMassachusetts General HospitalHarvard CatalystStiftelsen Kristian Gerhard JebsenFondation LeducqUniversity of MichiganMaze TherapeuticsAlnylam PharmaceuticalsNovo NordiskKorea Health Industry Development InstituteNational Institute for Health and Care ResearchHelse Midt-NorgeGlaxoSmithKlineBristol-Myers SquibbSchool of Public Health, University of MichiganAmerican Heart Association
KeywordsPreeclampsiaGestational hypertensionPregnancyGenome-wide association studyMedicineEclampsiaObstetricsBioinformaticsBiologyGeneticsSingle-nucleotide polymorphismGeneGenotype

Abstract

fetched live from OpenAlex

Abstract Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and offspring outcomes. Current tools for prediction, prevention, and treatment are limited. We tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and 703,117 controls and with gestational hypertension in 11,027 cases and 412,788 controls across discovery and follow-up cohorts using multi-ancestry meta-analysis. Altogether, we identified 18 independent loci associated with preeclampsia/eclampsia and/or gestational hypertension, 12 of which are novel (e.g., MTHFR-CLCN6 , WNT3A , NPR3 , PGR , and RGL3 ), including two loci ( PLCE1 , FURIN ) identified in multi-trait analysis. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development, and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external datasets, independent of first trimester risk markers. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and advance pregnancy risk stratification.

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)0.006
metaresearch head score (Gemma)0.012
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.033

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0060.012
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.009
Bibliometrics0.0020.003
Science and technology studies0.0010.000
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.062
GPT teacher head0.267
Teacher spread0.205 · 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 designMeta-analysis
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

Citations3
Published2022
Admission routes1
Has abstractyes

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Same venuemedRxiv→Same topicPregnancy and preeclampsia studies→French-language works237,207→