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Record W4402830588 · doi:10.1101/2024.09.23.24314240

Assessment of common genetic variation in Alzheimer’s and Parkinson’s diseases reveals global distinction in population attributable risk

2024· preprint· en· W4402830588 on OpenAlexafffund
Lietsel Jones, Catalina Cerquera‐Cleves, Artur FS Schuh, Mary B. Makarious, Hirotaka Iwaki, Mike A. Nalls, Alastair J. Noyce, Cornelis Blauwendraat, Andrew Singleton, Ignácio F. Mata, Sara Bandrés‐Ciga

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversité Laval
FundersNational Institute of Neurological Disorders and StrokeCanadian Institutes of Health ResearchNational Institute on AgingU.S. Department of Health and Human ServicesNational Institutes of HealthNational Human Genome Research Institute
KeywordsVariation (astronomy)Attributable riskGenetic variationPolygenic risk scorePopulationMedicineGeneticsBiologyEnvironmental healthGenotypeSingle-nucleotide polymorphismGene

Abstract

fetched live from OpenAlex

Abstract Emerging evidence suggests that the genetic architecture of Alzheimer’s (AD) and Parkinson’s diseases (PD) risk varies across ancestries. This study seeks to explore distinct and universal genetic targets across individuals of Latino, African/African Admixed, East Asian, and European populations by implementing Population Attributable Risk (PAR) comparisons on summary statistics from genome-wide association studies (GWAS). PAR was calculated for the most significant disease variants using summary statistics derived from select multi-ancestry GWAS meta-analyses, followed by fine-mapping analysis to validate genetic contribution of disease variants to European, African/African Admixed, East Asian, and Latino individuals. For both AD, APOE4 PAR estimates were universally high across all ancestries, with TSPAN14 and PICALM emerging as other common targets. Attributable risk varied across PD-related major risk loci including variation nearby GBA1 and LRRK2 . In contrast, SNCA, MCCC1, VPS13C , and MAPT loci demonstrated comparable attributable risk across ancestries. This cross-ancestry evaluation of PAR reinforces the genetic heterogeneity of AD and PD. In consideration of the complex etiology of these diseases, these findings may inform the strategic prioritization of therapeutic targets and improve global health outcomes.

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)0.005
metaresearch head score (Gemma)0.008
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 score0.005
Threshold uncertainty score0.025

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.008
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.020
GPT teacher head0.316
Teacher spread0.296 · 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

Citations2
Published2024
Admission routes2
Has abstractyes

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Same venuemedRxiv→Same topicGenetic Associations and Epidemiology→French-language works237,207→