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Resource Profile and User Guide of the Polygenic Index Repository

Joel Becker, View ORCID ProfileCasper A.P. Burik, Grant Goldman, Nancy Wang, Hariharan Jayashankar, Michael Bennett, View ORCID ProfileDaniel W. Belsky, View ORCID ProfileRichard Karlsson Linnér, View ORCID ProfileRafael Ahlskog, Aaron Kleinman, David A. Hinds, 23andMe Research Group, View ORCID ProfileAvshalom Caspi, David L. Corcoran, View ORCID ProfileTerrie E. Moffitt, Richie Poulton, Karen Sugden, Benjamin S. Williams, View ORCID ProfileKathleen Mullan Harris, View ORCID ProfileAndrew Steptoe, View ORCID ProfileOlesya Ajnakina, View ORCID ProfileLili Milani, Tõnu Esko, William G. Iacono, View ORCID ProfileMatt McGue, Patrik K.E. Magnusson, View ORCID ProfileTravis T. Mallard, View ORCID ProfileK. Paige Harden, View ORCID ProfileElliot M. Tucker-Drob, View ORCID ProfilePamela Herd, Jeremy Freese, View ORCID ProfileAlexander Young, View ORCID ProfileJonathan P. Beauchamp, Philipp Koellinger, Sven Oskarsson, View ORCID ProfileMagnus Johannesson, Peter M. Visscher, Michelle N. Meyer, David Laibson, David Cesarini, Daniel J. Benjamin, Patrick Turley, View ORCID ProfileAysu Okbay
doi: https://doi.org/10.1101/2021.05.08.443158
Joel Becker
1Department of Economics, New York University, New York, NY, USA
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Casper A.P. Burik
2Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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Grant Goldman
3National Bureau of Economic Research, Cambridge, MA, USA
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Nancy Wang
3National Bureau of Economic Research, Cambridge, MA, USA
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Hariharan Jayashankar
3National Bureau of Economic Research, Cambridge, MA, USA
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Michael Bennett
3National Bureau of Economic Research, Cambridge, MA, USA
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Daniel W. Belsky
4Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA
5Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA
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Richard Karlsson Linnér
2Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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Rafael Ahlskog
6Department of Government, Uppsala University, Uppsala, Sweden
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Aaron Kleinman
723andMe, Inc., Mountain View, CA, USA
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David A. Hinds
723andMe, Inc., Mountain View, CA, USA
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723andMe, Inc., Mountain View, CA, USA
Avshalom Caspi
8Department of Psychology and Neuroscience, Duke University, Durham, NC, USA
9Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
10Center for Genomic and Computational Biology, Duke University, Durham, NC, USA
11Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
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David L. Corcoran
10Center for Genomic and Computational Biology, Duke University, Durham, NC, USA
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Terrie E. Moffitt
8Department of Psychology and Neuroscience, Duke University, Durham, NC, USA
9Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
10Center for Genomic and Computational Biology, Duke University, Durham, NC, USA
11Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
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Richie Poulton
12Dunedin Multidisciplinary Health and Development Research Unit, University of Otago, Dunedin, Otago, New Zealand
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Karen Sugden
8Department of Psychology and Neuroscience, Duke University, Durham, NC, USA
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Benjamin S. Williams
8Department of Psychology and Neuroscience, Duke University, Durham, NC, USA
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Kathleen Mullan Harris
13Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC USA
14Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC USA
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Andrew Steptoe
15Department of Behavioural Science and Health, University College London, London, United Kingdom
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Olesya Ajnakina
15Department of Behavioural Science and Health, University College London, London, United Kingdom
16Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
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Lili Milani
17Institute of Genomics, University of Tartu, Tartu, Estonia
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Tõnu Esko
17Institute of Genomics, University of Tartu, Tartu, Estonia
18Broad Institute of MIT and Harvard, Cambridge, MA, USA
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William G. Iacono
19Department of Psychology, University of Minnesota, Minneapolis, MN, USA
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Matt McGue
19Department of Psychology, University of Minnesota, Minneapolis, MN, USA
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Patrik K.E. Magnusson
20Swedish Twin Registry, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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Travis T. Mallard
21Department of Psychology, The University of Texas at Austin, Austin, TX, USA
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K. Paige Harden
21Department of Psychology, The University of Texas at Austin, Austin, TX, USA
22Population Research Center, The University of Texas at Austin, Austin, TX, USA
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Elliot M. Tucker-Drob
21Department of Psychology, The University of Texas at Austin, Austin, TX, USA
22Population Research Center, The University of Texas at Austin, Austin, TX, USA
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Pamela Herd
23McCourt School of Public Policy, Georgetown University, Washington, DC, USA
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Jeremy Freese
24Department of Sociology, Stanford University, Stanford, CA, USA
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Alexander Young
25Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA
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Jonathan P. Beauchamp
26Interdisciplinary Center for Economic Science and Department of Economics, George Mason University, Fairfax, Virginia, USA
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Philipp Koellinger
2Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
27Robert M. La Follette School of Public Affairs, University of Wisconsin-Madison, Madison, WI, USA
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Sven Oskarsson
6Department of Government, Uppsala University, Uppsala, Sweden
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Magnus Johannesson
28Department of Economics, Stockholm School of Economics, Stockholm, Sweden
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Peter M. Visscher
29Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
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Michelle N. Meyer
30Center for Translational Bioethics and Health Care Policy, Geisinger Health System, Danville, PA, USA
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David Laibson
3National Bureau of Economic Research, Cambridge, MA, USA
31Department of Economics, Harvard University, Cambridge, MA, USA
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David Cesarini
1Department of Economics, New York University, New York, NY, USA
3National Bureau of Economic Research, Cambridge, MA, USA
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  • For correspondence: daniel.benjamin@gmail.com
Daniel J. Benjamin
3National Bureau of Economic Research, Cambridge, MA, USA
32UCLA Anderson School of Management, Los Angeles, CA, USA
33Human Genetics Department, UCLA David Geffen School of Medicine, Los Angeles, CA, USA
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Patrick Turley
18Broad Institute of MIT and Harvard, Cambridge, MA, USA
34Analytic Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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Aysu Okbay
2Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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  • For correspondence: daniel.benjamin@gmail.com
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Abstract

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is rapidly growing. 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 of which are novel—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 the additive SNP 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.

Competing Interest Statement

D.A.H., A.K., and members of the 23andMe Research Team are current or former employees of 23andMe, Inc. and hold stock or stock options in 23andMe.

Footnotes

  • ↵# These authors jointly directed the work.

  • https://github.com/JonJala/pgi_correct

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Resource Profile and User Guide of the Polygenic Index Repository
Joel Becker, Casper A.P. Burik, Grant Goldman, Nancy Wang, Hariharan Jayashankar, Michael Bennett, Daniel W. Belsky, Richard Karlsson Linnér, Rafael Ahlskog, Aaron Kleinman, David A. Hinds, 23andMe Research Group, Avshalom Caspi, David L. Corcoran, Terrie E. Moffitt, Richie Poulton, Karen Sugden, Benjamin S. Williams, Kathleen Mullan Harris, Andrew Steptoe, Olesya Ajnakina, Lili Milani, Tõnu Esko, William G. Iacono, Matt McGue, Patrik K.E. Magnusson, Travis T. Mallard, K. Paige Harden, Elliot M. Tucker-Drob, Pamela Herd, Jeremy Freese, Alexander Young, Jonathan P. Beauchamp, Philipp Koellinger, Sven Oskarsson, Magnus Johannesson, Peter M. Visscher, Michelle N. Meyer, David Laibson, David Cesarini, Daniel J. Benjamin, Patrick Turley, Aysu Okbay
bioRxiv 2021.05.08.443158; doi: https://doi.org/10.1101/2021.05.08.443158
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Resource Profile and User Guide of the Polygenic Index Repository
Joel Becker, Casper A.P. Burik, Grant Goldman, Nancy Wang, Hariharan Jayashankar, Michael Bennett, Daniel W. Belsky, Richard Karlsson Linnér, Rafael Ahlskog, Aaron Kleinman, David A. Hinds, 23andMe Research Group, Avshalom Caspi, David L. Corcoran, Terrie E. Moffitt, Richie Poulton, Karen Sugden, Benjamin S. Williams, Kathleen Mullan Harris, Andrew Steptoe, Olesya Ajnakina, Lili Milani, Tõnu Esko, William G. Iacono, Matt McGue, Patrik K.E. Magnusson, Travis T. Mallard, K. Paige Harden, Elliot M. Tucker-Drob, Pamela Herd, Jeremy Freese, Alexander Young, Jonathan P. Beauchamp, Philipp Koellinger, Sven Oskarsson, Magnus Johannesson, Peter M. Visscher, Michelle N. Meyer, David Laibson, David Cesarini, Daniel J. Benjamin, Patrick Turley, Aysu Okbay
bioRxiv 2021.05.08.443158; doi: https://doi.org/10.1101/2021.05.08.443158

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