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Record W3083079877 · doi:10.1101/2020.09.04.20187401

Using human genetics to understand the causes and consequences of circulating cardiac troponin I in the general population

2020· preprint· en· W3083079877 on OpenAlexaff
Marta R. Moksnes, Helge Røsjø, Anne Richmond, Magnus Nakrem Lyngbakken, Sarah E. Graham, Ailin Falkmo Hansen, Brooke N. Wolford, Sarah A. Gagliano Taliun, Jonathon LeFaive, Humaira Rasheed, Laurent F. Thomas, Wei Zhou, Ida Surakka, Nicholas J. Douville, Archie Campbell, David J. Porteous, Paul Welsh, Naveed Sattar, George Davey Smith, Lars G. Fritsche, Jonas B. Nielsen, Bjørn Olav Åsvold, Kristian Hveem, Caroline Hayward, Cristen J. Willer, Ben Brumpton, Torbjørn Omland

Bibliographic record

VenuemedRxiv · 2020
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsUniversité de MontréalMontreal Heart Institute
FundersNorwegian Institute of Public HealthNorges ForskningsrådHelse Midt-NorgeFakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige UniversitetNational Institutes of HealthFaculty of Medicine and Health, University of SydneyNorges Teknisk-Naturvitenskapelige Universitet
KeywordsMendelian randomizationTroponin IPopulationDiseaseMyocardial infarctionGenome-wide association studyInternal medicineTroponinCausal inferenceCardiologyMedicineGeneticsBiologyGeneGenetic variantsSingle-nucleotide polymorphismGenotypePathologyEnvironmental health

Abstract

fetched live from OpenAlex

Abstract Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study and perform a genome-wide association study of highsensitivity cTnI concentrations with 48 115 individuals. We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes: CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1 and LMAN1 . Using two-sample Mendelian randomization we confirmed the non-causal role of cTnI in acute myocardial infarction, but could not rule out a causal role for cTnI in heart failure. Using genetically informed methods for causal inference of cTnI helps inform the role and value of measuring cTnI in the general population.

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)0.002
metaresearch head score (Gemma)0.004
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.001
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 head0.101
GPT teacher head0.352
Teacher spread0.251 · 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
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

Citations0
Published2020
Admission routes1
Has abstractyes

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