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Record W3128153416 · doi:10.1038/s41588-021-00785-3

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

2021· article· en· W3128153416 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueNature Genetics · 2021
Typearticle
Languageen
FieldNeuroscience
TopicNeurological diseases and metabolism
Canadian institutionsHeart and Stroke FoundationSunnybrook Health Science CentreOccupational Cancer Research CentreHealth Sciences CentreMcGill UniversityMontreal Neurological Institute and HospitalUniversity of Toronto
FundersAdministration for Native AmericansTakeda Pharmaceuticals U.S.A.National Human Genome Research InstituteDemensförbundetNational Heart, Lung, and Blood InstituteNational Institute of Neurological Disorders and StrokeDepartment of Medicine, University of TorontoKing's College LondonCentre National de la Recherche ScientifiqueEuropean Regional Development FundNational Center for Advancing Translational SciencesMedical Research CouncilUniversity at BuffaloNational Institutes of HealthInstituto de Investigación Marqués de ValdecillaH. Lundbeck A/SUniversity of BristolIdorsia PharmaceuticalsJohns Hopkins UniversityCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasImperial College LondonUniversity of TorontoInstitut National de la Santé et de la Recherche MédicaleParkinson's UKCharles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. LouisNewcastle UniversityNational Institute on AgingNational Institute for Health and Care ResearchBiogenAgence Nationale de la RechercheSol Goldman Charitable TrustAmerican Parkinson Disease AssociationConsortium canadien en neurodégénérescence associée au vieillissementProthenaNorthwestern UniversitySunnybrook Research InstituteLittle Family FoundationCenter for Individualized Medicine, Mayo ClinicInstitute of Psychiatry, Psychology and Neuroscience, King’s College LondonLewy Body Dementia AssociationWellcome TrustFeinberg School of MedicineVirginia Commonwealth UniversityEli Lilly and CompanySorbonne UniversitéTheravance Biopharma USU.S. Department of Health and Human ServicesFoundation for the National Institutes of Health
KeywordsBiologyGenetic architectureComputational biologyLewy bodyGenome-wide association studyGeneticsGenomeDNA sequencingDementiaEvolutionary biologyGeneQuantitative trait locusDiseaseSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s disease and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition. Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

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.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.624
Threshold uncertainty score0.852

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.014
GPT teacher head0.247
Teacher spread0.233 · 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