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Record W4410477978 · doi:10.1101/2025.05.14.653986

An Updated Polygenic Index Repository: Expanded Phenotypes, New Cohorts, and Improved Causal Inference

2025· preprint· en· W4410477978 on OpenAlexaff
Robel Alemu, Anastasia Terskaya, Matthew D. Howell, Junming Guan, Aaron Kleinman, David Bann, Tim Morris, George B. Ploubidis, Emla Fitzsimons, Kathleen Mullan Harris, Avshalom Caspi, David L. Corcoran, Terrie E. Moffitt, Richie Poulton, Karen Sugden, Benjamin Williams, Andrew Steptoe, Olesya Ajnakina, Uku Vainik, Tõnu Esko, Archie Campbell, Caroline Hayward, William G. Iacono, Matt McGue, Robert F. Krueger, Anna R. Docherty, Andrey A. Shabalin, Ralph Hertwig, Philipp Koellinger, David Richter, Jan Goebel, Rafael Ahlskog, Sven Oskarsson, Patrik K. E. Magnusson, K. Paige Harden, Elliot M. Tucker–Drob, Charlotte K. L. Pahnke, Carlo Maj, Frank M. Spinath, Pamela Herd, Jeremy Freese, David Laibson, Michelle N. Meyer, Jonathan Jala, David Cesarini, Alexander I. Young, Patrick Turley, Daniel J. Benjamin, Aysu Okbay

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersNational Institute on AgingNational Institutes of HealthVetenskapsrådetEesti TeadusagentuurAmsterdam University Medical CentersOpen Philanthropy Project
KeywordsInterpretabilityLeverage (statistics)Statistical powerInferencePredictive powerConfoundingComputer scienceCausal inferencePhenotypeStatisticsData miningComputational biologyBiologyMachine learningMathematicsArtificial intelligenceGenetics

Abstract

fetched live from OpenAlex

Polygenic indexes (PGIs) - DNA-based predictors of individual phenotypes - have become essential tools across biomedical and social sciences. We introduce Version 2 of the Polygenic Index Repository, which expands phenotype coverage from 47 to 61, increases the number of participating datasets from 11 to 20, and adopts a more consistent and improved methodology for PGI construction. For 16 phenotypes, we leverage summary statistics from an updated GWAS meta-analysis with greater statistical power compared to the original release, thereby improving the PGI's predictive power. To improve power for family-based analyses, we provide imputed parental PGIs in all datasets with first-degree relatives and offer a framework for interpreting results from analyses that control for parental PGIs. We illustrate the utility of parental PGIs using two applications: (1) comparing PGI associations with and without parental PGI controls for all phenotypes in two Repository datasets with family data, and (2) for BMI and diastolic blood pressure, exploring the contribution of causal versus non-causal components of PGI associations to the imperfect portability of PGIs across subgroups within a genetic ancestry. Collectively, the updates enhance predictive performance, broaden the Repository's scope, and introduce novel resources that reduce confounding bias and improve interpretability.

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)0.021
metaresearch head score (Gemma)0.097
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.025
Threshold uncertainty score0.111

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0210.097
Meta-epidemiology (narrow)0.0020.002
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0070.011
Science and technology studies0.0010.001
Scholarly communication0.0050.003
Open science0.0050.005
Research integrity0.0020.004
Insufficient payload (model declined to judge)0.0250.009

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 head0.009
GPT teacher head0.243
Teacher spread0.234 · 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 designSimulation or modeling
Domainnot available
GenreMethods

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
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGenetic Associations and Epidemiology→French-language works237,207→