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Record W2885835268 · doi:10.1101/386680

Genome Wide Meta-Analysis identifies new loci associated with cardiac phenotypes and uncovers a common genetic signature shared by heart function and Alzheimer’s disease

2018· preprint· en· W2885835268 on OpenAlexfundno aff
MaEugenia Sáez, Antonio González‐Pérez, Begoña Hernández‐Olasagarre, Aida Beà, Sonia Moreno–Grau, Itziar de Rojas, Gemma C. Monté, Adela Orellana, Sergi Valero, Joan X. Comella, Daniel Sanchı́s, Agustı́n Ruiz

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEndoplasmic Reticulum Stress and Disease
Canadian institutionsnot available
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchGenentechNational Institutes of HealthNational Institute of Neurological Disorders and StrokeIXICOH. Lundbeck A/SCurePSPServierEisaiEuropean Federation of Pharmaceutical Industries and AssociationsNorthern California Institute for Research and EducationPfizerBiogenBioClinicaMayo Foundation for Medical Education and ResearchF. Hoffmann-La RocheUniversity of Southern CaliforniaMayo ClinicGlaxoSmithKlineU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbAlzheimer's AssociationNational Heart, Lung, and Blood InstituteNovartis Pharmaceuticals CorporationFoundation for the National Institutes of HealthEuropean CommissionAlzheimer's Disease Neuroimaging InitiativeMeso Scale Diagnostics
KeywordsGenome-wide association studyDiseasePhenotypeGenetic associationBiologyGeneHeart diseaseGeneticsGenetic architectureBioinformaticsSingle-nucleotide polymorphismMedicineGenotypeInternal medicine

Abstract

fetched live from OpenAlex

ABSTRACT Aims Echocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures of heart structure and functions have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with indicators of human cardiac function. This study started with the aim to investigate the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function. Methods and results Genome wide data from different studies were obtained from public repositories. After quality control and imputation, association analyses confirm the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer’s disease (AD). We further explored this unexpected observation which was confirmed by genetic correlation analyses. Conclusions Our findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimer’s disease.

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)0.004
metaresearch head score (Gemma)0.006
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 score0.004
Threshold uncertainty score0.023

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.006
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.010
Bibliometrics0.0040.006
Science and technology studies0.0010.000
Scholarly communication0.0030.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0040.000

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 head0.013
GPT teacher head0.217
Teacher spread0.204 · 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

Citations0
Published2018
Admission routes1
Has abstractyes

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