Resource profile and user guide of the Polygenic Index Repository

23andMe Research Group

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 (US)
JournalNature Human Behaviour
Volume5
Issue number12
Early online dateJun 17 2021
DOIs
StateE-pub ahead of print - Jun 17 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.

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