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Record W2508165250 · doi:10.1002/gepi.22064

The more you test, the more you find: The smallest <i>P</i>‐values become increasingly enriched with real findings as more tests are conducted

2017· article· en· W2508165250 on OpenAlexaff
Olga A. Vsevolozhskaya, Chia‐Ling Kuo, Gabriel Ruiz, Luda Diatchenko, Dmitri V. Zaykin

Bibliographic record

VenueGenetic Epidemiology · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersNational Institute of Environmental Health SciencesNational Institutes of Health
KeywordsStatistical hypothesis testingMultiple comparisons problemStatistical powerReplication (statistics)False discovery rateStatisticsSample size determinationGenome-wide association studyStatistical modelStatistical significanceBiologyGeneticsEconometricsMathematicsGeneSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

The increasing accessibility of data to researchers makes it possible to conduct massive amounts of statistical testing. Rather than follow specific scientific hypotheses with statistical analysis, researchers can now test many possible relationships and let statistics generate hypotheses for them. The field of genetic epidemiology is an illustrative case, where testing of candidate genetic variants for association with an outcome has been replaced by agnostic screening of the entire genome. Poor replication rates of candidate gene studies have improved dramatically with the increase in genomic coverage, due to factors such as adoption of better statistical practices and availability of larger sample sizes. Here, we suggest that another important factor behind the improved replicability of genome-wide scans is an increase in the amount of statistical testing itself. We show that an increase in the number of tested hypotheses increases the proportion of true associations among the variants with the smallest P-values. We develop statistical theory to quantify how the expected proportion of genuine signals (EPGS) among top hits depends on the number of tests. This enrichment of top hits by real findings holds regardless of whether genome-wide statistical significance has been reached in a study. Moreover, if we consider only those "failed" studies that produce no statistically significant results, the same enrichment phenomenon takes place: the proportion of true associations among top hits grows with the number of tests. The enrichment occurs even if the true signals are encountered at the logarithmically decreasing rate with the additional testing.

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)0.065
metaresearch head score (Gemma)0.346
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: Methods · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.935
Threshold uncertainty score0.344

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0650.346
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0080.007
Science and technology studies0.0010.010
Scholarly communication0.0070.010
Open science0.0030.004
Research integrity0.0040.007
Insufficient payload (model declined to judge)0.0100.003

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 head0.029
GPT teacher head0.316
Teacher spread0.287 · 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.

Study designSimulation or modeling
DomainMethods
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
Published2017
Admission routes1
Has abstractyes

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