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Record W3211973903 · doi:10.1101/2021.11.06.21265795

Genetic Contributions to Early and Late Onset Ischemic Stroke

2021· preprint· en· W3211973903 on OpenAlexaff
Thomas Jaworek, Huichun Xu, Brady Gaynor, John W. Cole, Kristiina Rannikmäe, Tara M. Stanne, Liisa Tomppo, Vida Abedi, Philippe Amouyel, Nicole D. Armstrong, John Attia, Steven Bell, Oscar Benavente, Giorgio B. Boncoraglio, Adam S. Butterworth, Jara Cárcel‐Márquez, Zhengming Chen, Michael Chong, Carlos Cruchaga, Mary Cushman, John Danesh, Stéphanie Debette, David Duggan, Jon Peter Durda, Gunnar Engström, Christian Enzinger, Jessica D. Faul, Natalie Fecteau, Israel Fernández‐Cadenas, Christian Geiger, Anne‐Katrin Giese, Raji P. Grewal, Ulrike Grittner, Aki S. Havulinna, Laura Heitsch, Marc C. Hochberg, Jie Hu, Andreea Ilinca, Marguerite R. Irvin, Rebecca D. Jackson, Mina A. Jacob, Raquel Rabionet, Jordi Jiménez-Conde, Julie A. Johnson, Sharon L.R. Kardia, Masaru Koido, Michiaki Kubo, Leslie A. Lange, Jin‐Moo Lee, Robin Lemmens, Christopher Levi, Jiang Li, Liming Li, Kuang Lin, Haley Lopez, Sothear Luke, Jane Maguire, Patrick F. McArdle, Caitrin W. McDonough, James F. Meschia, Tiina M. Metso, Martina Müller‐Nurasyid, Timothy D. O’Connor, Martin O’Donnell, Leema Reddy Peddareddygari, Joanna Pera, James A. Perry, Annette Peters, Jukka Putaala, Debashree Ray, Kathryn M. Rexrode, Marta Ribasés, Jonathan Rosand, Peter M. Rothwell, Tatjana Rundek, Kathleen A. Ryan, Ralph L. Sacco, Veikko Salomaa, Cristina Sánchez‐Mora, Reinhold Schmidt, Pankaj Sharma, Agnieszka Słowik, Jennifer A. Smith, Nicholas L. Smith, Sylvia Wassertheil‐Smoller, Martin Söderholm, O. Colin Stine, Daniel Strbian, Cathie Sudlow, Turgut Tatlisumak, Chikashi Terao, Vincent Thijs, Nuria P. Torres‐Aguila, David‐Alexandre Trégouët, Anil M. Tuladhar, Jan H. Veldink, Robin Walters, David R. Weir, Daniel Woo, Bradford B. Worrall, Charles C. Hong, Owen A. Ross, Ramin Zand, F-E de Leeuw, Guillaume Paré, Christopher D. Anderson, Hugh S. Markus, Christina Jern, Rainer Malik, Martin Dichgans, Braxton D. Mitchell, Steven J. Kittner

Bibliographic record

VenuemedRxiv · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcMaster UniversityPopulation Health Research InstituteThrombosis and Atherosclerosis Research InstituteUniversity of British Columbia
Fundersnot available
KeywordsABO blood group systemMedicineVenous thrombosisStroke (engine)Locus (genetics)Internal medicineIschemic strokeAge of onsetSNPCardiologyThrombosisSingle-nucleotide polymorphismBiologyGeneticsIschemiaDiseaseGenotypeGene

Abstract

fetched live from OpenAlex

Abstract Objective To determine the contribution of common genetic variants to risk of early onset ischemic stroke (IS). Methods We performed a meta-analysis of genome-wide association studies of early onset IS, ages 18-59, using individual level data or summary statistics in 16,927 cases and 576,353 non-stroke controls from 48 different studies across North America, Europe, and Asia. We further compared effect sizes at our most genome-wide significant loci between early and late onset IS and compared polygenic risk scores for venous thromboembolism between early versus later onset IS. Results We observed an association between early onset IS and ABO , a known stroke locus. The effect size of the peak ABO SNP, rs8176685, was significantly larger in early compared to late onset IS (OR 1.17 (95% C.I.: 1.11-1.22) vs 1.05 (0.99-1.12); p for interaction = 0.008). Analysis of genetically determined ABO blood groups revealed that early onset IS cases were more likely to have blood group A and less likely to have blood group O compared to both non-stroke controls and to late onset IS cases. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with early, compared to late, onset IS (p=0.008). Conclusion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with early onset IS, compared with late onset IS, supporting a stronger role of prothrombotic factors in early onset IS.

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)0.003
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.006
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.004
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.011
GPT teacher head0.272
Teacher spread0.262 · 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
Published2021
Admission routes1
Has abstractyes

Explore more

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