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 language | English |
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Pages (from-to) | 1744–1758 |
Number of pages | 15 |
Journal | Nature Human Behaviour |
Volume | 5 |
Issue number | December |
Early online date | 17 Jun 2021 |
DOIs | |
Publication status | Published - 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
Funders | Funder number |
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Pershing Square Fund | |
Ragnar Söderberg Foundation | E42/15 |
National Science Foundation | |
National Institutes of Health | |
National Institute on Drug Abuse | U01DA024417 |
National Institute on Aging | R01AG032282, 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 stiftelse | E9/11 |
Eunice Kennedy Shriver National Institute of Child Health and Human Development | R01 HD060726, R01 HD073342, R01-HD092548, P01 HD031921, R01HD083613, HD077482 |
Pershing Square Foundation | |
Horizon 2020 Framework Programme | MP1GI18418R, MMVCM18418R |
H2020 European Research Council | 647648 EdGe |
Open Philanthropy Project | |
Engineering Research Centers | 010623-00001 |
Ontario Genomics Institute | OGI-152 |
Social Sciences and Humanities Research Council of Canada | |
Medical Research Council | MR/P005918, G1002190 |
Economic and Social Research Council | ES/K005774/1 |
Australian Research Council | |
National Health and Medical Research Council | GNT113400 |
Health Research Council of New Zealand | |
Eesti Teadusagentuur | PRG184, PUT1660 |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | 016.Veni.198.058 |
Ministry of Business, Innovation and Employment | |
Jacobs Foundation | |
Vetenskapsrådet | 2019-00244 |
Riksbankens Jubileumsfond | P18-0782:1 |