Resource profile and user guide of the Polygenic Index Repository

23andMe Research Group

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Abstract

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies—some not previously published—from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.

Original languageEnglish
Pages (from-to)1744–1758
Number of pages15
JournalNature Human Behaviour
Volume5
Issue numberDecember
Early online date17 Jun 2021
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
The authors thank C. Shulman for helpful comments. This research was carried out under the auspices of the SSGAC. This research was conducted using the UKB resource under application number 11,425. J.B. was supported by the Pershing Square Fund of the Foundations of Human Behavior, awarded to D.L.; H.J., M.B., D.C. and P.T. by the Ragnar Söderberg Foundation (E42/15), to D.C.; C.A.P.B., P.K. and A.O. by an ERC Consolidator Grant (647648 EdGe), to P.K.; H.J., M.B., A.Y., J.P.B., M.N.M., D.C., D.J.B. and P.T. by Open Philanthropy (010623-00001), to D.J.B.; C.A.P.B., R.A. and S.O. by Riksbankens Jubileumsfond (P18-0782:1), to S.O.; C.A.P.B. and S.O. by the Swedish Research Council (2019-00244), to S.O.; G.G., N.W. and D.J.B. by the NIA/NIH

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Funding

The authors thank C. Shulman for helpful comments. This research was carried out under the auspices of the SSGAC. This research was conducted using the UKB resource under application number 11,425. J.B. was supported by the Pershing Square Fund of the Foundations of Human Behavior, awarded to D.L.; H.J., M.B., D.C. and P.T. by the Ragnar Söderberg Foundation (E42/15), to D.C.; C.A.P.B., P.K. and A.O. by an ERC Consolidator Grant (647648 EdGe), to P.K.; H.J., M.B., A.Y., J.P.B., M.N.M., D.C., D.J.B. and P.T. by Open Philanthropy (010623-00001), to D.J.B.; C.A.P.B., R.A. and S.O. by Riksbankens Jubileumsfond (P18-0782:1), to S.O.; C.A.P.B. and S.O. by the Swedish Research Council (2019-00244), to S.O.; G.G., N.W. and D.J.B. by the NIA/NIH

FundersFunder number
Pershing Square Fund
Ragnar Söderberg FoundationE42/15
National Science Foundation
National Institutes of Health
National Institute on Drug AbuseU01DA024417
National Institute on AgingR01AG032282, AG-21079, R01AG041868, K99-AG062787-01, R01-AG042568, R56-AG058726, AG-9775, R01 AG017644, 5U01-MH109539-02, R24-AG065184, 1R01-MH101244-02, R01AG049789, AG-033285
Spencer Foundation
University of Wisconsin-Madison
Ragnar Söderbergs stiftelseE9/11
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentR01 HD060726, R01 HD073342, R01-HD092548, P01 HD031921, R01HD083613, HD077482
Pershing Square Foundation
Horizon 2020 Framework ProgrammeMP1GI18418R, MMVCM18418R
H2020 European Research Council647648 EdGe
Open Philanthropy Project
Engineering Research Centers010623-00001
Ontario Genomics InstituteOGI-152
Social Sciences and Humanities Research Council of Canada
Medical Research CouncilMR/P005918, G1002190
Economic and Social Research CouncilES/K005774/1
Australian Research Council
National Health and Medical Research CouncilGNT113400
Health Research Council of New Zealand
Eesti TeadusagentuurPRG184, PUT1660
Nederlandse Organisatie voor Wetenschappelijk Onderzoek016.Veni.198.058
Ministry of Business, Innovation and Employment
Jacobs Foundation
Vetenskapsrådet2019-00244
Riksbankens JubileumsfondP18-0782:1

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