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Towards Reproducible Brain-Wide Association Studies

View ORCID ProfileScott Marek, Brenden Tervo-Clemmens, Finnegan J. Calabro, David F. Montez, Benjamin P. Kay, Alexander S. Hatoum, Meghan Rose Donohue, William Foran, Ryland L. Miller, Eric Feczko, Oscar Miranda-Dominguez, Alice M. Graham, Eric A. Earl, Anders J. Perrone, Michaela Cordova, Olivia Doyle, Lucille A. Moore, Greg Conan, Johnny Uriarte, Kathy Snider, Angela Tam, Jianzhong Chen, Dillan J. Newbold, Annie Zheng, Nicole A. Seider, Andrew N. Van, Timothy O. Laumann, Wesley K. Thompson, Deanna J. Greene, Steven E. Petersen, Thomas E. Nichols, View ORCID ProfileB.T. Thomas Yeo, Deanna M. Barch, Hugh Garavan, Beatriz Luna, Damien A. Fair, Nico U.F. Dosenbach
doi: https://doi.org/10.1101/2020.08.21.257758
Scott Marek
1Departments of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110
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  • ORCID record for Scott Marek
  • For correspondence: smarek@wustl.edu ndosenbach@wustl.edu
Brenden Tervo-Clemmens
8Departments of Psychology, University of Pittsburgh, Pittsburgh, PA 15213
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Finnegan J. Calabro
9Departments of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213
10Departments of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213
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David F. Montez
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
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Benjamin P. Kay
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
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Alexander S. Hatoum
1Departments of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110
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Meghan Rose Donohue
1Departments of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110
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William Foran
9Departments of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213
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Ryland L. Miller
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
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Eric Feczko
11Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN 55455
12Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455
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Oscar Miranda-Dominguez
11Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN 55455
12Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455
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Alice M. Graham
14Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239
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Eric A. Earl
11Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN 55455
14Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239
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Anders J. Perrone
11Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN 55455
14Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239
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Michaela Cordova
14Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239
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Olivia Doyle
14Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239
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Lucille A. Moore
14Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239
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Greg Conan
11Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN 55455
14Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239
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Johnny Uriarte
14Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239
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Kathy Snider
14Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239
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Angela Tam
15Department of Electrical and Computer Engineering, National University of Singapore, Singapore
16Centre for Sleep and Cognition, National University of Singapore, Singapore
17Clinical Imaging Research Center, National University of Singapore, Singapore
18Clinical Imaging Research Center, National University of Singapore, Singapore
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Jianzhong Chen
15Department of Electrical and Computer Engineering, National University of Singapore, Singapore
16Centre for Sleep and Cognition, National University of Singapore, Singapore
17Clinical Imaging Research Center, National University of Singapore, Singapore
18Clinical Imaging Research Center, National University of Singapore, Singapore
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Dillan J. Newbold
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
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Annie Zheng
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
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Nicole A. Seider
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
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Andrew N. Van
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
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Timothy O. Laumann
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
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Wesley K. Thompson
21Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA
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Deanna J. Greene
21Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA
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Steven E. Petersen
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
3Departments of Radiology, Washington University School of Medicine, St. Louis, MO 63110
4Departments of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63110
6Departments of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110
7Psychological and Brain Sciences, Washington University School of Medicine, St. Louis, MO 63110
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Thomas E. Nichols
23Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Population Health, University of Oxford, Oxford, UK
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B.T. Thomas Yeo
15Department of Electrical and Computer Engineering, National University of Singapore, Singapore
16Centre for Sleep and Cognition, National University of Singapore, Singapore
17Clinical Imaging Research Center, National University of Singapore, Singapore
18Clinical Imaging Research Center, National University of Singapore, Singapore
19N.1 Institute for Health, Institute for Digital Medicine, National University of Singapore, Singapore
20NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore
21Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA
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  • ORCID record for B.T. Thomas Yeo
Deanna M. Barch
1Departments of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110
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Hugh Garavan
24Department of Psychiatry, University of Vermont, Burlington, VT 05401
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Beatriz Luna
8Departments of Psychology, University of Pittsburgh, Pittsburgh, PA 15213
9Departments of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213
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Damien A. Fair
11Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN 55455
12Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455
13Institute of Child Development, University of Minnesota Medical School, Minneapolis, MN 55455
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Nico U.F. Dosenbach
2Departments of Neurology, Washington University School of Medicine, St. Louis, MO 63110
3Departments of Radiology, Washington University School of Medicine, St. Louis, MO 63110
4Departments of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63110
5Departments of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110
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  • For correspondence: smarek@wustl.edu ndosenbach@wustl.edu
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Abstract

Magnetic resonance imaging (MRI) continues to drive many important neuroscientific advances. However, progress in uncovering reproducible associations between individual differences in brain structure/function and behavioral phenotypes (e.g., cognition, mental health) may have been undermined by typical neuroimaging sample sizes (median N=25)1,2. Leveraging the Adolescent Brain Cognitive Development (ABCD) Study3 (N=11,878), we estimated the effect sizes and reproducibility of these brain-wide associations studies (BWAS) as a function of sample size. The very largest, replicable brain-wide associations for univariate and multivariate methods were r=0.14 and r=0.34, respectively. In smaller samples, typical for brain-wide association studies (BWAS), irreproducible, inflated effect sizes were ubiquitous, no matter the method (univariate, multivariate). Until sample sizes started to approach consortium-levels, BWAS were underpowered and statistical errors assured. Multiple factors contribute to replication failures4–6; here, we show that the pairing of small brain-behavioral phenotype effect sizes with sampling variability is a key element in wide-spread BWAS replication failure. Brain-behavioral phenotype associations stabilize and become more reproducible with sample sizes of N⪆2,000. While investigator-initiated brain-behavior research continues to generate hypotheses and propel innovation, large consortia are needed to usher in a new era of reproducible human brain-wide association studies.

Competing Interest Statement

Nico Dosenbach and Damien Fair are co-founders of Nous Imaging

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Towards Reproducible Brain-Wide Association Studies
Scott Marek, Brenden Tervo-Clemmens, Finnegan J. Calabro, David F. Montez, Benjamin P. Kay, Alexander S. Hatoum, Meghan Rose Donohue, William Foran, Ryland L. Miller, Eric Feczko, Oscar Miranda-Dominguez, Alice M. Graham, Eric A. Earl, Anders J. Perrone, Michaela Cordova, Olivia Doyle, Lucille A. Moore, Greg Conan, Johnny Uriarte, Kathy Snider, Angela Tam, Jianzhong Chen, Dillan J. Newbold, Annie Zheng, Nicole A. Seider, Andrew N. Van, Timothy O. Laumann, Wesley K. Thompson, Deanna J. Greene, Steven E. Petersen, Thomas E. Nichols, B.T. Thomas Yeo, Deanna M. Barch, Hugh Garavan, Beatriz Luna, Damien A. Fair, Nico U.F. Dosenbach
bioRxiv 2020.08.21.257758; doi: https://doi.org/10.1101/2020.08.21.257758
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Towards Reproducible Brain-Wide Association Studies
Scott Marek, Brenden Tervo-Clemmens, Finnegan J. Calabro, David F. Montez, Benjamin P. Kay, Alexander S. Hatoum, Meghan Rose Donohue, William Foran, Ryland L. Miller, Eric Feczko, Oscar Miranda-Dominguez, Alice M. Graham, Eric A. Earl, Anders J. Perrone, Michaela Cordova, Olivia Doyle, Lucille A. Moore, Greg Conan, Johnny Uriarte, Kathy Snider, Angela Tam, Jianzhong Chen, Dillan J. Newbold, Annie Zheng, Nicole A. Seider, Andrew N. Van, Timothy O. Laumann, Wesley K. Thompson, Deanna J. Greene, Steven E. Petersen, Thomas E. Nichols, B.T. Thomas Yeo, Deanna M. Barch, Hugh Garavan, Beatriz Luna, Damien A. Fair, Nico U.F. Dosenbach
bioRxiv 2020.08.21.257758; doi: https://doi.org/10.1101/2020.08.21.257758

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