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Record W3105414758 · doi:10.1101/239269

Atrial Fibrillation Genetic Risk Differentiates Cardioembolic Stroke from other Stroke Subtypes

2017· preprint· en· W3105414758 on OpenAlexaff
Sara L. Pulit, Lu‐Chen Weng, Patrick F. McArdle, Ludovic Trinquart, Seung Hoan Choi, Braxton D. Mitchell, Jonathan Rosand, P. Bakker, Emelia J. Benjamin, Patrick T. Ellinor, Steven J. Kittner, Steven A. Lubitz, Christopher D. Anderson, Ingrid E. Christophersen, Michiel Rienstra, Carolina Roselli, Xiaoyan Yin, Bastiaan Geelhoed, John Barnard, Honghuang Lin, Dan E. Arking, Albert V. Smith, Christine M. Albert, Mark Chaffin, Nathan R. Tucker, Molong Li, Derek Klarin, Nathan A. Bihlmeyer, Siew‐Kee Low, Peter Weeke, Martina Müller‐Nurasyid, J. G. Smith, Jennifer A. Brody, Maartje N. Niemeijer, Marcus Dörr, Stella Trompet, Jennifer E. Huffman, Stefan Gustafsson, Claudia Schurmann, Marcus E. Kleber, Leo‐Pekka Lyytikäinen, Ilkka Seppälä, Rainer Malik, A.R.V.R. Horimoto, Marco Pérez, Juha Sinisalo, Stefanie Aeschbacher, Sébastien Thériault, Jie Yao, Farid Radmanesh, Stefan Weiß, Alexander Teumer, Sebastian Clauß, Rajat Deo, Daniel J. Rader, Svati Shah, Joylene E. Siland, Michiaki Kubo, Jonathan D. Smith, David R. Van Wagoner, Joshua C. Bis, Siegfried Perz, Bruce M. Psaty, Paul M. Ridker, Jared W. Magnani, Tamara B. Harris, Lenore J. Launer, M. Benjamin Shoemaker, Sandosh Padmanabhan, Jeffrey Haessler, Traci M. Bartz, Mélanie Waldenberger, Peter Lichtner, Marina Arendt, José Eduardo Krieger, Mika Kähönen, Lorenz Risch, Alfredo José Mansur, Annette Peters, Blair H. Smith, Lars Lind, Stuart A. Scott, Yingchang Lu, Erwin B. Bottinger, Jussi Hernesniemi, Cecilia M. Lindgren, Jorge Wong, Jie Huang, Markku Eskola, Andrew P. Morris, Ian Ford, Alex P. Reiner, Graciela Delgado, Lin Y. Chen, Yii‐Der Ida Chen, Roopinder K. Sandhu, Man Li, Eric Boerwinkle, Lewin Eisele, Lars Lannfelt, Natalia S. Rost, Olle Melander, Anders Hamsten, Jan Heeringa, Joshua C. Denny, Jennifer Kriebel, Dawood Darbar, Christopher Newton‐Cheh, Christian M. Shaffer, Peter W. Macfarlane, Stefanie Heilmann‐Heimbach, Peter Almgren, Paul L. Huang, Nona Sotoodehnia, Elsayed Z. Soliman, André G. Uitterlinden, Albert Hofman, Oscar H. Franco, Uwe Völker, Karl-Heinz Jöckel, Moritz F. Sinner, Henry J. Lin, Xiuqing Guo, Martin Dichgans, Erik Ingelsson, Charles Kooperberg, Ruth J. F. Loos, Jari Laurikka, David Conen, Pim van der Harst, Marja‐Liisa Lokki, Sekar Kathiresan, Alexandre C. Pereira, J. Wouter Jukema, Caroline Hayward, Jerome I. Rotter, Winfried März, Terho Lehtimäki, Bruno H. Stricker, Mina K. Chung, Stephan B. Felix, Vilmundur Guðnason, Álvaro Alonso, Dan M. Roden, Albert Y. Sun, Stefan Kääb, Jemma C. Hopewell, Stéphanie Debette, Ganesh Chauhan, Qiong Yang, Bradford B. Worrall, Guillaume Paré, Yanick Hagemeijer, Niek Verweij, Kent D. Taylor, A.M. Campbell, Patrik K. E. Magnusson, David J. Porteous, Lynne J. Hocking, Efthymia Vlachopoulou, Nancy L. Pedersen, Kjell Nikus, Daniel I. Chasman, Susan R. Heckbert, Toshihiro Tanaka, Kathryn L. Lunetta, Sylvia Smoller, John D. Sorkin, Xingwu Wang, Magdy Selim, Aleksandra Pikula, Philip A. Wolf, Sudha Seshadri, Paul I. W. de Bakker, Kathryn M. Rexrode, Ida Chen, May M. Luke, Michelle Sale, Tsong‐Hai Lee, Ku‐Chou Chang, Mitchell S Elkind, Larry B. Goldstein, Michael Luke James, Monique M.B. Breteler, Chris O’Donnell, Didier Leys, Cara L. Carty, Chelsea S. Kidwell, Jes Olesen, Pankaj Sharma, Stephen S. Rich, Turgot Tatlisumak, Olli Häppölä, Philippe Bijlenga, Eva Giralt, Jaume Roquer, Jordi Jiménez-Conde, Ioana Cotlarcius, John Hardy, Michał Korostyński, Giorgio B. Boncoraglio, Elena Ballabio, Eugenio Parati, Adamski Mateusz, Andrzej Urbanik, Tomasz Dziedzic, Jeremiasz Jagiełła, Jerzy Gąsowski, Marcin Wnuk, Rafael Olszanecki, Joanna Pera, Agnieszka Słowik, Karol Juchniewicz, Christopher Levi, Paul Nyquist, Íscia Lopes‐Cendes, Norberto L. Cabral, Paulo Henrique Condeixa de França, Anderson Gonçalves, Lina Keller, Milita Crisby, Konstantinos Kostulas, Robin Lemmens, Kourosh R. Ahmadi, Christian Opherk, Marco Duering, Mariya Gonik, Julie Staals, Philippe Burri, Ariane Sadr‐Nabavi, Javier Romero, Alessandro Biffi, Chris Anderson, Guido J. Falcone, Bart Brouwers, Rose Du, Christina Kourkoulis, Thomas W.K. Battey, James F. Meschia, Thomas G. Brott, Alexander Pichler, Christian Enzinger, Helena Schmidt, Reinhold Schmidt, Stephan Seiler, Susan H. Blanton, Yoshiji Yamada, Anna Bersano, Tatjana Rundek, Ralph Sacco, Yu‐Feng Yvonne Chan, Andreas Gschwendtner, Zhen Deng, Taura L. Barr, Katrina Gwinn, Roderick A. Corriveau, Andrew Singleton, Salina P. Waddy, Christopher Chen, Kim En Le, Wei Ling Lee, Eng‐King Tan, Akintomi Olugbodi, Peter M. Rothwell, Sabrina Schilling, Vincent Mok, Elena R. Lebedeva, Christina Jern, Katarina Jood, Sandra Olsson, Helen Kim, Chaeyoung Lee, Laura L. Kilarski, Hugh Markus, Jennifer Peycke, Steve Bevan, Wayne H.-H. Sheu, Hung‐Yi Chiou, Joseph Chern, Elias A. Giraldo, Muhammad Taqi, Vivek Jain, Olivia Lam, George Howard, Daniel Woo, John W. Cole, Jeff O’Connell, Dianna M. Milewicz, Kachikwu Illoh, Colin O Stine, Bartosz Karaszewski, David J. Werring, Reecha Sofat, June Smalley, Björn M. Hansen, Bo Norrving, Gustav Smith, Juan José Díaz, Vincent Thijs, Femke van’t Hof, Ale Algra, Mary Joan MacLeod, Rodney T. Perry, Donna K. Arnett, Alessandro Pezzini, Alessandro Padovani, Steve Cramer, Mark Fisher, Danish Saleheen, Joseph P. Broderick, Brett Kissela, Alex S. F. Doney, Sudlow Cathie, Kristiina Rannikmäe, Scott Silliman, Caitrin Rowe McDonough, Matthew Walters, Annie Pedersén, Kazuma Nakagawa, Christy Chang, Mark Dobbins, Yu-Ching Chang, Robert Brown, Devin Brown, Raj N. Kalaria, Jane Maguire, Attia John, Martin Farrall, Anne‐Katrin Giese, Myriam Fornage, Jennifer J. Majersik, Mary Cushman, Keith L. Keene, Siiri Bennett, David Tirschwell, W. T. Longstreth, J. David Spence, Joan Montaner, Israel Fernández‐Cadenas, Carl D. Langefeld, Cheryl Bushnell, Laura Heitsch, Jin‐Moo Lee, Kevin N. Sheth

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2017
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversity of AlbertaHamilton Health SciencesMcMaster UniversityPopulation Health Research Institute
Fundersnot available
KeywordsStroke (engine)Atrial fibrillationMedicineInternal medicineCardiologyLacunar strokeOdds ratioIschemic stroke

Abstract

fetched live from OpenAlex

Abstract Objective We sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk. Methods We evaluated genetic correlations between a prior genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously-validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. Results We observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson’s r=0.77 and 0.76, respectively, across SNPs with p < 4.4 × 10 −4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45×10 −48 ), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per sd = 1.07, p = 0.004), but no other primary stroke subtypes (all p > 0.1). Conclusions Genetic risk for AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

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)0.005
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 score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.005
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.012
GPT teacher head0.232
Teacher spread0.220 · 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

Citations10
Published2017
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGenetic Associations and Epidemiology→French-language works237,207→