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Record W2891085289 · doi:10.1038/s41467-018-04989-w

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

2018· review· en· W2891085289 on OpenAlexaff
Molly Went, Amit Sud, Asta Försti, Britt-Marie Halvarsson, Niels Weinhold, Scott Kimber, Mark van Duin, Guðmar Þorleifsson, Amy Holroyd, David C. Johnson, Li Ni, Giulia Orlando, Philip Law, Mina Ali, Bowang Chen, Jonathan S. Mitchell, Daníel F. Guðbjartsson, Rowan Kuiper, Owen Stephens, Uta Bertsch, Peter Broderick, C Campo, Obul Reddy Bandapalli, Hermann Einsele, Walter A. Gregory, Urban Gullberg, Jens Hillengaß, Per Hoffmann, Graham Jackson, Karl‐Heinz Jöckel, Ellinor Johnsson, Sigurður Y. Kristinsson, Ulf‐Henrik Mellqvist, Hareth Nahi, Douglas F. Easton, Paul D.P. Pharoah, Alison M. Dunning, Julian Peto, Federico Canzian, Anthony J. Swerdlow, Rosalind A. Eeles, Zsofia Kote‐Jarai, Kenneth Muir, Nora Pashayan, Jolanta Nickel, Markus M. Nöthen, Þórunn Rafnar, Fiona M. Ross, Miguel Inácio da Silva Filho, Hauke Thomsen, Ingemar Turesson, Annette Juul Vangsted, Niels Frost Andersen, Anders Waage, Brian A. Walker, Anna‐Karin Wihlborg, Annemiek Broyl, Faith E. Davies, Unnur Þorsteinsdóttir, Christian Langer, Markus Hansson, Hartmut Goldschmidt, Martin Kaiser, Pieter Sonneveld, Kāri Stefánsson, Gareth J. Morgan, Kari Hemminki, Björn Nilsson, Richard S. Houlston, Brian E. Henderson, Christopher A. Haiman, Sara Benlloch, Fredrick R. Schumacher, Ali Amin Al Olama, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen J. Chanock, Victoria L. Stevens, Catherine M. Tangen, Jyotsna Batra, Judith Clements, Henrik Grönberg, Johanna Schleutker, Demetrius Albanes, Stephanie J. Weinstein, Alicja Wolk, Catharine West, Lorelei A. Mucci, Géraldine Cancel‐Tassin, Stella Koutros, Karina D. Sørensen, Eli Marie Grindedal, David E. Neal, Freddie C. Hamdy, Jenny Donovan, Ruth C. Travis, Robert J. Hamilton, Sue A. Ingles, Barry S. Rosenstein, Yong‐Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Hermann Brenner, Christiane Maier, Jeri Kim, Esther M. John, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Hassan Abdul Razack, Lisa F. Newcomb, Davor Lessel, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Manuela Gago-Domínguez, Monique J. Roobol, F. Ménégaux, Kay‐Tee Khaw, Lisa Cannon‐Albright, Hardev Pandha, Stephen N. Thibodeau

Bibliographic record

VenueNature Communications · 2018
Typereview
Languageen
FieldMedicine
TopicMultiple Myeloma Research and Treatments
Canadian institutionsUniversity of AlbertaPrincess Margaret Cancer Centre
FundersDivision of Cancer Epidemiology and Genetics, National Cancer InstituteNational Heart, Lung, and Blood InstituteMedical Research CouncilHellenic Health FoundationMutuelle Générale de l'Education NationaleSvenska LäkaresällskapetCenter for Translational Molecular MedicineDeutsche KrebshilfeAssociazione Italiana per la Ricerca sul CancroVetenskapsrådetWorld Cancer Research FundStavros Niarchos FoundationNational Cancer InstituteKnut och Alice Wallenbergs StiftelseKarolinska InstitutetBlood Cancer UKMarcus och Amalia Wallenbergs minnesfondInstitut Gustave-RoussyEuropean Hematology AssociationStiftelsen för Strategisk ForskningUniversity of LeedsDeutsche ForschungsgemeinschaftNational Institutes of HealthHeinz Nixdorf StiftungRosetrees TrustEuropean CommissionBundesministerium für Bildung und ForschungNational Institute for Health and Care ResearchQueensland University of TechnologyUniversity of CambridgeWellcome TrustUniversity of Southern CaliforniaCancer Research UKLigue Contre le CancerDeutsches KrebsforschungszentrumNational Institute of General Medical SciencesDeutsches Zentrum für Neurodegenerative ErkrankungenAustralian Prostate Cancer ResearchNational Cancer Research InstituteLunds UniversitetInstituto de Salud Carlos IIIAmgenCentre International de Recherche sur le CancerInstitut National de la Santé et de la Recherche MédicaleMultiple Myeloma Research FoundationCase Western Reserve UniversityCancer Research Institute
KeywordsGenome-wide association studyEpigeneticsBiologyGeneticsGenetic associationBiological pathwayComputational biologymicroRNAGene expression profilingGeneAutophagyGene expressionSingle-nucleotide polymorphismApoptosisGenotype

Abstract

fetched live from OpenAlex

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.

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)0.001
metaresearch head score (Gemma)0.005
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.970
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.002
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 head0.051
GPT teacher head0.382
Teacher spread0.330 · 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 designOther design
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

Citations114
Published2018
Admission routes1
Has abstractyes

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