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Record W4381189914 · doi:10.1016/j.xgen.2023.100345

Multi-ancestry meta-analysis identifies 5 novel loci for ischemic stroke and reveals heterogeneity of effects between sexes and ancestries

2023· article· en· W4381189914 on OpenAlexfundno aff
Ida Surakka, Kuan-Han Wu, Whitney Hornsby, Brooke N. Wolford, Fred Shen, Wei Zhou, Jennifer E. Huffman, Anita Pandit, Yao Hu, Ben Brumpton, Anne Heidi Skogholt, Maiken E. Gabrielsen, Robin Walters, Kristian Hveem, Charles Kooperberg, Sebastian Zöllner, Peter W.F. Wilson, Nadia R. Sutton, Mark J. Daly, Benjamin M. Neale, Cristen J. Willer

Bibliographic record

VenueCell Genomics · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related molecular mechanisms research
Canadian institutionsnot available
FundersFaculté de médecine et des sciences de la santé, Université de SherbrookeFakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige UniversitetMedical School, University of MichiganNorwegian Institute of Public HealthNational Institutes of HealthTaiwan BiobankNorges ForskningsrådSt. Olavs Hospital Universitetssykehuset i TrondheimHelse Midt-NorgeSchool of Public Health, University of MichiganStiftelsen Kristian Gerhard JebsenNorges Teknisk-Naturvitenskapelige UniversitetBiometQIMR Berghofer Medical Research InstituteFaculty of Medicine and Health, University of SydneyUniversity of California, Los AngelesUniversity of Michigan
KeywordsBiobankGenome-wide association studyStroke (engine)Locus (genetics)Genetic heterogeneityGeneticsMeta-analysisBiologyGenetic associationIschemic strokeMedicineGenotypeBioinformaticsInternal medicineSingle-nucleotide polymorphismGeneIschemia

Abstract

fetched live from OpenAlex

Stroke is the second leading cause of death and disability worldwide. Stroke prevalence varies by sex and ancestry, possibly due to genetic heterogeneity between subgroups. We performed a genome-wide meta-analysis of 16 biobanks across multiple ancestries to study the genetics of ischemic stroke (60,176 cases, 1,310,725 controls) as part of the Global Biobank Meta-analysis Initiative (GBMI) and further combined the results with previously published MegaStroke. Five novel loci for ischemic stroke (LAMC1, CALCRL, PLSCR1, CDKN1A, and SWAP70) were identified after replication in four additional datasets. One previously reported locus showed significant ancestry heterogeneity (ABO), and one showed significant sex heterogeneity (ALDH2). The ALDH2 association was male specific (males p = 1.67e−24, females p = 0.126) and was additionally observed only in the East Asian ancestry (male) samples. These findings emphasize the need for more diverse datasets with large sample sizes to further understand the genetic predisposition of stroke in different ancestry and sex groups.

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)0.009
metaresearch head score (Gemma)0.014
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.048

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0090.014
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0040.017
Bibliometrics0.0030.004
Science and technology studies0.0010.001
Scholarly communication0.0030.001
Open science0.0010.002
Research integrity0.0010.001
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 head0.071
GPT teacher head0.328
Teacher spread0.257 · 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 designMeta-analysis
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

Citations21
Published2023
Admission routes1
Has abstractyes

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