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Record W2898243427 · doi:10.1101/454249

Heritability and genetic variance of dementia with Lewy bodies

2018· preprint· en· W2898243427 on OpenAlexafffund
Rita Guerreiro, Valentina Escott‐Price, Dena G. Hernandez, Célia Kun‐Rodrigues, Owen A. Ross, Tatiana Orme, João Luís Neto, Susana Carmona, Nadia Dehghani, John D. Eicher, Claire E. Shepherd, Laura Parkkinen, Lee Darwent, Michael G. Heckman, Sonja W. Scholz, Juan C. Troncoso, Olga Pletnikova, Ted M. Dawson, Liana S. Rosenthal, Olaf Ansorge, Jordi Clarimón, Alberto Lleó, Estrella Morenas‐Rodríguez, Lorraine N. Clark, Lawrence S. Honig, Karen Marder, Afina W. Lemstra, Ekaterina Rogaeva, Peter St George‐Hyslop, Elisabet Londos, Henrik Zetterberg, Imelda Barber, Anne Braae, Kristelle Brown, Kevin Morgan, Claire Troakes, Safa Al‐Sarraj, Tammaryn Lashley, Janice L. Holton, Yaroslau Compta, Vivianna M. Van Deerlin, Geidy E. Serrano, Thomas G. Beach, Suzanne Lesage, Douglas Galasko, Eliezer Masliah, Isabel Santana, Pau Pástor, Mónica Díez-Fairén, Miquel Aguilar, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Tamás Révész, Andrew J. Lees, Bradley F. Boeve, Ronald C. Petersen, Tanis J. Ferman, Caroline Graff, Nigel J. Cairns, John C. Morris, Stuart Pickering‐Brown, David Mann, Glenda M. Halliday, John Hardy, John Q. Trojanowski, Dennis W. Dickson, Andrew Singleton, David J. Stone, José Brás

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsOccupational Cancer Research CentreUniversity of Toronto
FundersNational Institute of Environmental Health SciencesNational Institute of Neurological Disorders and StrokeNational Institute on AgingNIHR Oxford Biomedical Research CentreNational Health and Medical Research CouncilMedical Research CouncilNational Institutes of HealthHjartaverndInstitute of GeneticsAgence Nationale de la RechercheAssistance publique-Hôpitaux de ParisHersenstichtingParkinson's Disease FoundationMcGill UniversityUniversity of DundeeSamfundet FolkhälsanBundesministerium für Bildung und ForschungLandspítali HáskólasjúkrahúsKrembil FoundationUniversity of TorontoGeneralitat de CatalunyaInstitut National de la Santé et de la Recherche MédicaleParkinson's UKFolkhälsanin TutkimussäätiöNational Institute for Health and Care ResearchAlzheimer SocietyAlzheimer's SocietyUniversité de LilleUniversity of California, San DiegoJohns Hopkins UniversityDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's diseaseUniversity College London Hospitals NHS Foundation TrustEU Joint Programme – Neurodegenerative Disease ResearchErasmus Medisch CentrumNeuroscience Research AustraliaUniversity College LondonWellcome TrustMemorial University of NewfoundlandUniversity of New South WalesConsortium canadien en neurodégénérescence associée au vieillissementUniversity of PennsylvaniaU.S. Department of Veterans AffairsU.S. Department of DefenseHelene Morgan Babcock and Alfred Babcock Memorial Scholarship TrustCentre hospitalier régional universitaire de LilleHelsingin YliopistoCentres de Recerca de CatalunyaHelsingin ja Uudenmaan SairaanhoitopiiriLittle Family FoundationAmerican Parkinson Disease AssociationAlzheimer's AssociationParkinson VerenigingMichael J. Fox Foundation for Parkinson's ResearchNational Heart, Lung, and Blood InstituteItä-Suomen YliopistoMayo ClinicU.S. Department of Health and Human Services
KeywordsHeritabilityDementia with Lewy bodiesGenome-wide association studyBiologyLinkage disequilibriumGenetic correlationSingle-nucleotide polymorphismGenetic variationGenetic associationGeneticsDiseaseSNPGenetic architectureDementiaAllelePhenotypeEvolutionary biologyGenotypeMedicineGeneInternal medicine

Abstract

fetched live from OpenAlex

Abstract Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson’s disease (PD) or Alzheimer’s disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.

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)0.001
metaresearch head score (Gemma)0.003
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 score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.010
GPT teacher head0.218
Teacher spread0.208 · 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

Citations6
Published2018
Admission routes2
Has abstractyes

Explore more

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