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Record W3000668058 · doi:10.1101/2020.01.17.910497

Trans-ethnic and ancestry-specific blood-cell genetics in 746,667 individuals from 5 global populations

2020· preprint· en· W3000668058 on OpenAlexaff
Ming‐Huei Chen, Laura M. Raffield, Abdou Mousas, Saori Sakaue, Jennifer E. Huffman, Tao Jiang, Parsa Akbari, Dragana Vuckovic, Erik L. Bao, Arden Moscati, Xue Zhong, Regina Manansala, Véronique Laplante, Minhui Chen, Ken Sin Lo, Huijun Qian, Caleb A. Lareau, Mélissa Beaudoin, Masato Akiyama, Traci M. Bartz, Yoav Ben‐Shlomo, Andrew D Beswick, Jette Bork‐Jensen, Erwin P. Böttinger, Jennifer A. Brody, Frank J.A. van Rooij, Kumaraswamy Naidu Chitrala, Kelly Cho, Hélène Choquet, Adolfo Correa, John Danesh, Emanuele Di Angelantonio, Niki Dimou, Jingzhong Ding, Paul Elliott, Tõnu Esko, Michele K. Evans, James S. Floyd, Linda Broer, Niels Grarup, Michael H. Guo, Andreas Greinacher, Jeff Haessler, Torben Hansen, Joanna M. M. Howson, Wei Huang, Eric Jorgenson, Tim Kacprowski, Mika Kähönen, Masahiro Kanai, Savita Karthikeyan, Leslie A. Lange, Terho Lehtimäki, Markus M. Lerch, Allan Linneberg, Ching‐Ti Liu, Leo-Pekka Lyytikäinen, Ani Manichaikul, Koichi Matsuda, Karen L. Mohlke, Nina Mononen, Yoshinori Murakami, Girish N. Nadkarni, Matthias Nauck, Kjell Nikus, Willem H. Ouwehand, Nathan Pankratz, Oluf Pedersen, Michael Preuß, Bruce M. Psaty, Olli Raitakari, David J. Roberts, Stephen S. Rich, Blanca Rodríguez, Jonathan D. Rosen, Jerome I. Rotter, Petra Schubert, Cassandra N. Spracklen, Praveen Surendran, Hua Tang, Jean‐Claude Tardif, Mohsen Ghanbari, Uwe Völker, Henry Völzke, Nicholas A. Watkins, Alan B. Zonderman, VA Million Veteran Program, Peter W.F. Wilson, Yun Li, Adam S. Butterworth, Jean‐François Gauchat, Charleston W. K. Chiang, Bingshan Li, Ruth J. F. Loos, William J. Astle, Evangelos Evangelou, Vijay G. Sankaran, Yukinori Okada, Nicole Soranzo, Andrew D. Johnson, Alex P. Reiner, Paul L. Auer, Guillaume Lettre

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversité de MontréalMontreal Heart Institute
Fundersnot available
KeywordsBiologyGeneticsGenetic architectureGenome-wide association studyGenetic associationGenetic genealogyEthnic groupTraitPhenotypeGeneGenotypePopulationDemographySingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

SUMMARY Most loci identified by GWAS have been found in populations of European ancestry (EA). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EA individuals, we identified 5,552 trait-variant associations at P <5×10 −9 , including 71 novel loci not found in EA populations. We also identified novel ancestry-specific variants not found in EA, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL7 secretion levels in vitro . Fine-mapping prioritized variants annotated as functional, and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EA-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations, and compared genetic architecture and the impact of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.395
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
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 head0.044
GPT teacher head0.271
Teacher spread0.227 · 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 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

Citations63
Published2020
Admission routes1
Has abstractyes

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