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Record W4281666919 · doi:10.1038/s41591-022-01835-x

Transferability of genetic risk scores in African populations

2022· article· en· W4281666919 on OpenAlexaff
Abram Bunya Kamiza, Sounkou M. Touré, Marijana Vujković, Tafadzwa Machipisa, Opeyemi Soremekun, Christopher Kintu, Manuel Corpas, Fraser Pirie, Elizabeth Young, Dipender Gill, Manjinder S. Sandhu, Pontiano Kaleebu, Moffat Nyirenda, Ayesha A. Motala, Tinashe Chikowore, Segun Fatumo

Bibliographic record

VenueNature Medicine · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsPopulation Health Research InstituteMcMaster University
FundersFogarty International CenterVictor Daitz FoundationGovernment of the United KingdomServierWellcomeImperial College LondonNational Institute for Health and Care ResearchSt. George's, University of LondonSouth African Medical Research CouncilOffice of Research and DevelopmentBritish Heart FoundationNational Human Genome Research InstituteWellcome TrustMedical Research CouncilLondon School of Hygiene and Tropical MedicineNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsTransferabilityPopulationDemographyZuluBiologyGeographyMedicineStatisticsEnvironmental healthMathematics

Abstract

fetched live from OpenAlex

Abstract The poor transferability of genetic risk scores (GRSs) derived from European ancestry data in diverse populations is a cause of concern. We set out to evaluate whether GRSs derived from data of African American individuals and multiancestry data perform better in sub-Saharan Africa (SSA) compared to European ancestry-derived scores. Using summary statistics from the Million Veteran Program (MVP), we showed that GRSs derived from data of African American individuals enhance polygenic prediction of lipid traits in SSA compared to European and multiancestry scores. However, our GRS prediction varied greatly within SSA between the South African Zulu (low-density lipoprotein cholesterol (LDL-C), R 2 = 8.14%) and Ugandan cohorts (LDL-C, R 2 = 0.026%). We postulate that differences in the genetic and environmental factors between these population groups might lead to the poor transferability of GRSs within SSA. More effort is required to optimize polygenic prediction in Africa.

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)0.001
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.015
Threshold uncertainty score0.279

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.012
GPT teacher head0.290
Teacher spread0.278 · 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.

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

Citations117
Published2022
Admission routes1
Has abstractyes

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