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Record W4384923561 · doi:10.1186/s40246-023-00514-3

Characterizing the polygenic architecture of complex traits in populations of East Asian and European descent

2023· article· en· W4384923561 on OpenAlexaff
Antonella De Lillo, Frank R. Wendt, Gita A. Pathak, Renato Polimanti

Bibliographic record

VenueHuman Genomics · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsPublic Health OntarioUniversity of Toronto
FundersNational Institute on Deafness and Other Communication DisordersNational Institute on Drug AbuseNational Center for Advancing Translational SciencesNational Institute of Mental HealthOne Mind
KeywordsBiologyBiobankSingle-nucleotide polymorphismGenetic architectureGeneticsQuantitative trait locusGenome-wide association studyPhenotypeTraitDemographyGenotypeGene

Abstract

fetched live from OpenAlex

Abstract To investigate the polygenicity of complex traits in populations of East Asian (EAS) and European (EUR) descents, we leveraged genome-wide data from Biobank Japan, UK Biobank, and FinnGen cohorts. Specifically, we analyzed up to 215 outcomes related to 18 health domains, assessing their polygenic architecture via descriptive statistics, such as the proportion of susceptibility SNPs per trait ( π c ). While we did not observe EAS–EUR differences in the overall distribution of polygenicity parameters across the phenotypes investigated, there were ancestry-specific patterns in the polygenicity differences between health domains. In EAS, pairwise comparisons across health domains showed enrichment for π c differences related to hematological and metabolic traits (hematological fold-enrichment = 4.45, p = 2.15 × 10 –7 ; metabolic fold-enrichment = 4.05, p = 4.01 × 10 –6 ). For both categories, the proportion of susceptibility SNPs was lower than that observed for several other health domains (EAS-hematological median π c = 0.15%, EAS-metabolic median π c = 0.18%) with the strongest π c difference with respect to respiratory traits (EAS-respiratory median π c = 0.50%; hematological- p = 2.26 × 10 –3 ; metabolic- p = 3.48 × 10 –3 ). In EUR, pairwise comparisons showed multiple π c differences related to the endocrine category (fold-enrichment = 5.83, p = 4.76 × 10 –6 ), where these traits showed a low proportion of susceptibility SNPs (EUR-endocrine median π c = 0.01%) with the strongest difference with respect to psychiatric phenotypes (EUR-psychiatric median π c = 0.50%; p = 1.19 × 10 –4 ). Simulating sample sizes of 1,000,000 and 5,000,000 individuals, we also showed that ancestry-specific polygenicity patterns translate into differences across health domains in the genetic variance explained by susceptibility SNPs projected to be genome-wide significant (e.g., EAS hematological-neoplasm p = 2.18 × 10 –4 ; EUR endocrine-gastrointestinal p = 6.80 × 10 –4 ). These findings highlight that traits related to the same health domains may present ancestry-specific variability in their polygenicity.

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)0.002
metaresearch head score (Gemma)0.002
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 score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.002
Science and technology studies0.0000.000
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 head0.055
GPT teacher head0.279
Teacher spread0.225 · 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

Citations4
Published2023
Admission routes1
Has abstractyes

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