MétaCan
Menu
Back to cohort
Record W2779204423 · doi:10.1212/wnl.0000000000004853

Genetic variation in <i>CFH</i> predicts phenytoin-induced maculopapular exanthema in European-descent patients

2017· article· en· W2779204423 on OpenAlexfundno aff
Mark McCormack, Hongsheng Gui, Andrés Ingason, Doug Speed, Galen E.B. Wright, Eunice J. Zhang, Rodrigo Secolin, Clarissa Lin Yasuda, Maxwell Kwok, Stefan Wolking, Sarah Rau, Andreja Avberšek, Kristin Heggeli, Costin Leu, Chantal Depondt, Graeme J. Sills, Anthony G Marson, Pauls Auce, Martin J. Brodie, Ben Francis, Michael R. Johnson, Bobby P.C. Koeleman, Pasquale Striano, Antonietta Coppola, Federico Zara, Wolfram S. Kunz, Josemir W. Sander, Holger Lerche, Karl Martin Klein, Sarah Weckhuysen, Martin Krenn, Lárus J. Gudmundsson, Roland Krause, Neil H. Shear, Colin J.D. Ross, Norman Delanty, Munir Pirmohamed, Bruce Carleton, Íscia Lopes‐Cendes, Wei‐Ping Liao, Terence J. O’Brien, Sanjay M. Sisodiya, Stacey S. Cherny, Patrick Kwan, Samuel F. Berkovic, Daniel H. Lowenstein, Erin L. Heinzen, Håkon Håkonarson, Russell J. Buono, Karen Oliver, Honsheng Gui, Joseph Willis, Anna Tostevin, Krishna Chinthapalli, Mojgansadat Borghei, Sinéad B. Heavin, Christian Hengsbach, Yvonne Weber, Zvonka Rener Primec, Antonio Gamberdella, Amedeo Bianchi, Giuseppe Capovilla, Anna Teresa Giallonardo, Angela La Neve, Giovanni Crichiutt, Aglaia Vignoli, Roberto Michelucci, Francesca Bisulli, Carla Marini, Belcastro Vicenzo, Sarah R. Langley, Andrea Jorgensen, Prashant K. Srivastava, Fritz Zimprich, Ekaterina Pataraia, Felix Rosenow, Hiltrud Muhle, Dieter Dennig, Bernhard J. Steinhoff, Susanne Schubert‐Bast, Hartmut Baier, Rikke S. Møller, Marina Nikanorova, Peter De Jonghe, Hannah Stamberger, Bianca Berghuis, Anja C. M. Sonsma, Carolien G. F. de Kovel, David B. Goldstein, Slavé Petrovski, Rodney A. Radtke, Michael R. Hayden, Stuart MacLeod, Reza Ghannadan, Shahrad R. Rassekh, Henk Visscher, Folefac Aminkeng, Michelle Higginson, Nasim Massah, Fudan Miao, Adrienne E. Borrie, Ursula Amstutz, Claudette Hildebrand, Shevaun Hughes, Kaitlyn Shaw, Satvir Dhoot, Amit P. Bhavsar, Y Li, Jong Wook Lee, Kaarina Kowalec, Jessica Stortz, Tessa Bendyshe-Walton, Mikaela K. Barker, Duncan Waltrip, Rachel Bader, Britt I. Drögemöller, Nicole McGoldrick, Cheri Nijssen‐Jordan, David C. Johnson, Carnation Zhuwaki, Linda Verbeek, Rick Kaczowka, Patti Stevenson, Kevin Hall, Nick Honcharik, Geert ‘t Jong, Sara J. Israels, Shanna Chan, Byron Garnham, Michelle Staub, Michael Rieder, Becky Malkin, Gideon Koren, Shinya Ito, Paul Nathan, Mark Greenberg, Miho Inoue, Sachi Sakaguchi, Toshihiro Tanaka, Hisaki Fujii, Mina Ogawa, Taro Kamiya, Smita Karande, Sholeh Ghayoori, Régis Vaillancourt, Donna L. Johnston, Herpreet Mankoo, Elaine Wong, Brenda J. Wilson, Lauren O’Connor, Caleb Hui, Cindy Yuen, Andrea Walsh, Kaviyarasan Mahalingam, Jean‐François Bussières, Denis Lebel, Pierre Barret, Aurélie Clauson, Ève Courbon, L. Cerruti, Maud Harry, Marine Aussedat, Margaret Murray, Marilyn Tiller, C. K. Osborne

Bibliographic record

VenueNeurology · 2017
Typearticle
Languageen
FieldMedicine
TopicDrug-Induced Adverse Reactions
Canadian institutionsnot available
FundersHealth and Medical Research FundMedical Research CouncilCanadian Institutes of Health ResearchUniversitair Ziekenhuis AntwerpenEpilepsy SocietyHáskóli ÍslandsEisaiUniversità degli Studi di GenovaEberhard Karls Universität TübingenMinistry of Education of the People's Republic of ChinaFundação de Amparo à Pesquisa do Estado de São PauloScience Foundation IrelandNovartis PharmaEuropean CommissionStichting Epilepsie Instellingen NederlandGlaxoSmithKlineImperial College LondonBC Children's HospitalNational Institute for Health and Care ResearchUniversity of TorontoUniversity College LondonLi Ka Shing Faculty of Medicine, University of Hong KongRoyal College of Surgeons in IrelandUCB PharmaValeant Pharmaceuticals InternationalUniversität WienGuangzhou Medical UniversityPhilipps-Universität MarburgUniversité du LuxembourgMedizinische Universität WienUniversitair Medisch Centrum UtrechtAmgenPfizerRheinische Friedrich-Wilhelms-Universität BonnUniversiteit AntwerpenCanadian Dermatology Foundation
KeywordsPhenytoinVariation (astronomy)Genetic variationMedicineDescent (aeronautics)Genetic variantsGeneticsGenotypeBiologyGeneEpilepsyPsychiatry

Abstract

fetched live from OpenAlex

<h3>Objective</h3> To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. <h3>Methods</h3> We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. <h3>Results</h3> We report an association between a rare variant in the complement factor H–related 4 (<i>CFHR4</i>) gene and phenytoin-induced MPE in Europeans (<i>p</i> = 4.5 × 10<sup>–11</sup>; odds ratio [95% confidence interval] 7 [3.2–16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (<i>CFH</i>) gene. In addition, our results reinforce the association between <i>HLA-A*31:01</i> and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. <h3>Conclusions</h3> The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H–related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients.

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 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)0.000
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 score0.113
Threshold uncertainty score0.769

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.022
GPT teacher head0.261
Teacher spread0.239 · 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 teacher head, 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

Citations40
Published2017
Admission routes1
Has abstractyes

Explore more

Same venueNeurologySame topicDrug-Induced Adverse ReactionsFrench-language works237,207