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Record W2169555151 · doi:10.1038/ncomms6068

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

2014· review· en· W2169555151 on OpenAlexaff
Iris Postmus, Stella Trompet, Harshal Deshmukh, Michael R. Barnes, Xiaohui Li, Helen R. Warren, Daniel I. Chasman, Kaixin Zhou, Benoît J. Arsenault, Louise A. Donnelly, Kerri L. Wiggins, Christy L. Avery, Paula J. Griffin, QiPing Feng, Kent D. Taylor, Guo Li, Daniel S. Evans, Albert V. Smith, Catherine E. de Keyser, Andrew D. Johnson, Anton J. M. de Craen, David J. Stott, Brendan M. Buckley, Ian Ford, Rudi G. J. Westendorp, P. Eline Slagboom, Naveed Sattar, Patricia B. Munroe, Peter Sever, Neil Poulter, Alice Stanton, Denis C. Shields, Eoin OʼBrien, Sue Shaw‐Hawkins, Yu Chen, Deborah A. Nickerson, Joshua D. Smith, Marie‐Pierre Dubé, S. Matthijs Boekholdt, G. Kees Hovingh, John J.P. Kastelein, Paul McKeigue, John Betteridge, Andrew Neil, Paul N. Durrington, Alex S. F. Doney, Fiona Carr, Andrew P. Morris, Mark I. McCarthy, Leif Groop, Emma Ahlqvist, Joshua C. Bis, Kenneth Rice, Nicholas L. Smith, Thomas Lumley, Eric A. Whitsel, Til Stürmer‎, Eric Boerwinkle, Julius S. Ngwa, Christopher J. O’Donnell, Ramachandran S. Vasan, Wei‐Qi Wei, Russell A. Wilke, Ching‐Ti Liu, Fangui Sun, Xiuqing Guo, Susan R. Heckbert, Wendy S. Post, Nona Sotoodehnia, Alice M. Arnold, Jeanette M. Stafford, Jingzhong Ding, David M. Herrington, Stephen B. Kritchevsky, Guðný Eiríksdóttir, Leonore J. Launer, Tamara B. Harris, Audrey Y. Chu, Franco Giulianini, Jean MacFadyen, Bryan J. Barratt, Fredrik Nyberg, Bruno H. Stricker, André G. Uitterlinden, Albert Hofman, Fernando Rivadeneira, Valur Emilsson, Oscar H. Franco, Paul M. Ridker, Vilmundur Guðnason, Joshua C. Denny, Christie M. Ballantyne, Jerome I. Rotter, L. Adrienne Cupples, Bruce M. Psaty, Jean‐Claude Tardif, Helen M. Colhoun, G. A. Hitman, Ronald M. Krauss, J. Wouter Jukema, Mark J. Caulfield, Peter Donnelly, Inês Barroso, Jenefer M. Blackwell, Elvira Bramon, Matthew A. Brown, Juan P. Casas, Aiden Corvin, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Robert Plomin, Anna Rautanen, Stephen Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas Wood, Gavin Band, Céline Bellenguez, Colin L. Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard D. Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Sarah Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T McCann, Jennifer Liddle, Simon Potter, Rathi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul A. Weston, Sara Widaa, Pamela Whittaker

Bibliographic record

VenueNature Communications · 2014
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversité de MontréalMontreal Heart Institute
FundersNational Center for Research ResourcesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of General Medical SciencesNational Institute for Health and Care ResearchNational Institute on AgingNational Center for Advancing Translational SciencesMedical Research CouncilNational Institutes of HealthU.S. Public Health ServiceHjartaverndErasmus Medisch CentrumSchool of Medicine, Boston UniversityEuropean CommissionNational Institute of Neurological Disorders and StrokeBritish Heart FoundationNational Human Genome Research InstituteWellcome TrustMinisterie van Onderwijs, Cultuur en WetenschapImperial College LondonJohns Hopkins UniversityErasmus Universiteit RotterdamBristol-Myers SquibbAstraZenecaZonMwWake Forest UniversityNational Heart, Lung, and Blood InstitutePfizerDiabetes UK
KeywordsPharmacogeneticsGenome-wide association studyLdl cholesterolMeta-analysisStatinCholesterolComputational biologyDrug responseHydroxymethylglutaryl-CoA Reductase InhibitorsGenetic associationMedicineBioinformaticsBiologyGeneticsPharmacologyInternal medicineGenotypeGeneSingle-nucleotide polymorphismDrug

Abstract

fetched live from OpenAlex

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.

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)0.003
metaresearch head score (Gemma)0.008
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.806
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.008
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.000
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 head0.126
GPT teacher head0.450
Teacher spread0.324 · 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.

Study designMeta-analysis
Domainnot available
GenreReview

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

Citations279
Published2014
Admission routes1
Has abstractyes

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