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Record W4384924290 · doi:10.1007/s12265-023-10411-8

Age and Sex Differences in the Genetics of Cardiomyopathy

2023· article· en· W4384924290 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.
aboutThe title or abstract carries a Canadian signal from the geographic lexicon.

Bibliographic record

VenueJournal of Cardiovascular Translational Research · 2023
Typearticle
Languageen
FieldMedicine
TopicCardiomyopathy and Myosin Studies
Canadian institutionsTed Rogers Centre for Heart ResearchChildren's Hospital of Eastern OntarioUniversity Health NetworkSickKids FoundationUniversity of TorontoKingston General HospitalLondon Health Sciences CentreMcMaster Children's HospitalHospital for Sick Children
FundersWellcome TrustHospital for Sick ChildrenCanadian Institutes of Health ResearchNational Institute for Health and Care ResearchCancer Research UKHeart and Stroke Foundation of Canada
KeywordsPenetranceMYH7CardiomyopathyDilated cardiomyopathyHypertrophic cardiomyopathyLMNAMedicineGeneticsGenotypeInternal medicineBiologyGeneMutationPhenotypeHeart failure

Abstract

fetched live from OpenAlex

Cardiomyopathy has variable penetrance. We analyzed age and sex-related genetic differences in 1,397 cardiomyopathy patients (Ontario, UK) with whole genome sequencing. Pediatric cases (n = 471) harbored more deleterious protein-coding variants in Tier 1 cardiomyopathy genes compared to adults (n = 926) (34.6% vs 25.9% respectively, p = 0.0015), with variant enrichment in constrained coding regions. Pediatric patients had a higher burden of sarcomere and lower burden of channelopathy gene variants compared to adults. Specifically, pediatric patients had more MYH7 and MYL3 variants in hypertrophic cardiomyopathy, and fewer TTN truncating variants in dilated cardiomyopathy. MYH7 variants clustered in the myosin head and neck domains in children. OBSCN was a top mutated gene in adults, enriched for protein-truncating variants. In dilated cardiomyopathy, female patients had a higher burden of z-disc gene variants compared to males. Genetic differences may explain age and sex-related variability in cardiomyopathy penetrance. Genotype-guided predictions of age of onset can inform pre-test genetic counseling. Pediatric cardiomyopathy patients were more likely to be genotype-positive than adults with a higher burden of variants in MYH7, MYL3, TNNT2, VCL. Adults had a higher burden of OBSCN and TTN variants. Females with dilated cardiomyopathy (DCM) had a higher burden of z-disc gene variants compared to males.

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.

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)0.007
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.438
Threshold uncertainty score0.250

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0070.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
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 head0.135
GPT teacher head0.372
Teacher spread0.237 · 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