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Scott A. Marek, Brenden Tervo‐Clemmens, Finnegan J. Calabro, David F. Montez, Benjamin P. Kay, Alexander Samir Hatoum, Meghan Rose Donohue, Will Foran, Ryland L. Miller, Timothy John Hendrickson and 35 more
Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions 1–3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping 4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain–behavioural phenotype associations 5,6 . Here we used three of the largest neuroimaging datasets currently available—with a total sample size of around 50,000 individuals—to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain–phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.
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Marek, S. A., Tervo‐Clemmens, B., Calabro, F. J., Montez, D. F., Kay, B. P., Hatoum, A. S., Donohue, M. R., Foran, W., Miller, R. L., Hendrickson, T. J., Malone, S. M., Kandala, S., Feczko, E., Miranda-Domínguez, Ó., Graham, A. M., Earl, E., Perrone, A. J., Cordova, M., Doyle, O. J., … Dosenbach, N. U. (2022). Reproducible brain-wide association studies require thousands of individuals. Nature, 603(7902), 654–660. https://doi.org/10.1038/s41586-022-04492-9
Marek, Scott A., et al. "Reproducible brain-wide association studies require thousands of individuals." Nature, vol. 603, no. 7902, 2022, pp. 654–660, https://doi.org/10.1038/s41586-022-04492-9.
Marek, Scott A., Brenden Tervo‐Clemmens, Finnegan J. Calabro, David F. Montez, Benjamin P. Kay, Alexander Samir Hatoum, Meghan Rose Donohue, et al. "Reproducible brain-wide association studies require thousands of individuals." Nature 603, no. 7902 (2022): 654–660. https://doi.org/10.1038/s41586-022-04492-9.
Marek S. A., Tervo‐Clemmens B., Calabro F. J. [и др.] Reproducible brain-wide association studies require thousands of individuals // Nature. — 2022. — Vol. 603, № 7902. — P. 654–660. — URL: https://doi.org/10.1038/s41586-022-04492-9
@article{marek2022reproducible,
title = {{Reproducible brain-wide association studies require thousands of individuals}},
author = {Scott A. Marek and Brenden Tervo‐Clemmens and Finnegan J. Calabro and David F. Montez and Benjamin P. Kay and Alexander Samir Hatoum and Meghan Rose Donohue and Will Foran and Ryland L. Miller and Timothy John Hendrickson and Stephen M. Malone and Sridhar Kandala and Eric Feczko and Óscar Miranda-Domínguez and Alice M. Graham and Eric Earl and Anders J. Perrone and Michaela Cordova and Olivia J. Doyle and Lucille A. Moore and Greg Conan and Johnny Uriarte and Kathy Snider and Benjamin J. Lynch and James C. Wilgenbusch and Thomas Pengo and Angela Tam and Jianzhong Chen and Dillan J. Newbold and Annie Zheng and Nicole A. Seider and Andrew N. Van and Athanasia Metoki and Roselyne J. Chauvin and Timothy O. Laumann and Deanna J. Greene and Steven E. Petersen and Hugh Garavan and Wesley Kurt Thompson and Thomas E. Nichols and B.T. Thomas Yeo and Deanna M. Barch and Beatríz Luna and Damien A. Fair and Nico U.F. Dosenbach},
journal = {Nature},
year = {2022},
volume = {603},
number = {7902},
pages = {654--660},
doi = {10.1038/s41586-022-04492-9},
url = {https://doi.org/10.1038/s41586-022-04492-9}
}TY - JOUR AU - Marek, Scott A. AU - Tervo‐Clemmens, Brenden AU - Calabro, Finnegan J. AU - Montez, David F. AU - Kay, Benjamin P. AU - Hatoum, Alexander Samir AU - Donohue, Meghan Rose AU - Foran, Will AU - Miller, Ryland L. AU - Hendrickson, Timothy John AU - Malone, Stephen M. AU - Kandala, Sridhar AU - Feczko, Eric AU - Miranda-Domínguez, Óscar AU - Graham, Alice M. AU - Earl, Eric AU - Perrone, Anders J. AU - Cordova, Michaela AU - Doyle, Olivia J. AU - Moore, Lucille A. AU - Conan, Greg AU - Uriarte, Johnny AU - Snider, Kathy AU - Lynch, Benjamin J. AU - Wilgenbusch, James C. AU - Pengo, Thomas AU - Tam, Angela AU - Chen, Jianzhong AU - Newbold, Dillan J. AU - Zheng, Annie AU - Seider, Nicole A. AU - Van, Andrew N. AU - Metoki, Athanasia AU - Chauvin, Roselyne J. AU - Laumann, Timothy O. AU - Greene, Deanna J. AU - Petersen, Steven E. AU - Garavan, Hugh AU - Thompson, Wesley Kurt AU - Nichols, Thomas E. AU - Yeo, B.T. Thomas AU - Barch, Deanna M. AU - Luna, Beatríz AU - Fair, Damien A. AU - Dosenbach, Nico U.F. TI - Reproducible brain-wide association studies require thousands of individuals JO - Nature VL - 603 IS - 7902 SP - 654 EP - 660 PY - 2022 DA - 2022/03/16 DO - 10.1038/s41586-022-04492-9 UR - https://doi.org/10.1038/s41586-022-04492-9 ER -
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