Reproducible brain-wide association studies require thousands of individuals.
Autor: | Marek S; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. smarek@wustl.edu., Tervo-Clemmens B; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. btervo-clemmens@mgh.harvard.edu.; Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA. btervo-clemmens@mgh.harvard.edu., Calabro FJ; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA., Montez DF; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Kay BP; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Hatoum AS; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA., Donohue MR; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA., Foran W; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA., Miller RL; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Hendrickson TJ; University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN, USA., Malone SM; Department of Psychology, University of Minnesota, Minneapolis, MN, USA., Kandala S; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA., Feczko E; Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA.; Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA., Miranda-Dominguez O; Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA.; Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA., Graham AM; Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA., Earl EA; Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA.; Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA., Perrone AJ; Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA.; Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA., Cordova M; Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA., Doyle O; Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA., Moore LA; Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA., Conan GM; Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA.; Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA., Uriarte J; Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA., Snider K; Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA., Lynch BJ; Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA.; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA., Wilgenbusch JC; Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA.; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA., Pengo T; University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN, USA., Tam A; Department of Electrical and Computer Engineering, National University of Singapore, Singapore, Singapore.; Centre for Sleep and Cognition, National University of Singapore, Singapore, Singapore.; Centre for Translational MR Research, National University of Singapore, Singapore, Singapore.; N.1 Institute for Health, Institute for Digital Medicine, National University of Singapore, Singapore, Singapore., Chen J; Department of Electrical and Computer Engineering, National University of Singapore, Singapore, Singapore.; Centre for Sleep and Cognition, National University of Singapore, Singapore, Singapore.; Centre for Translational MR Research, National University of Singapore, Singapore, Singapore.; N.1 Institute for Health, Institute for Digital Medicine, National University of Singapore, Singapore, Singapore., Newbold DJ; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Zheng A; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Seider NA; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Van AN; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.; Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, USA., Metoki A; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Chauvin RJ; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA., Laumann TO; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA., Greene DJ; Department of Cognitive Science, University of California San Diego, La Jolla, CA, USA., Petersen SE; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.; Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, USA.; Department of Radiology, Washington University School of Medicine, St Louis, MO, USA.; Department of Neurological Surgery, Washington University School of Medicine, St Louis, MO, USA.; Department of Psychological and Brain Sciences, Washington University in St Louis, St Louis, MO, USA., Garavan H; Department of Psychiatry, University of Vermont, Burlington, VT, USA., Thompson WK; Division of Biostatistics, University of California San Diego, La Jolla, CA, USA., Nichols TE; Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Yeo BTT; Department of Electrical and Computer Engineering, National University of Singapore, Singapore, Singapore.; Centre for Sleep and Cognition, National University of Singapore, Singapore, Singapore.; Centre for Translational MR Research, National University of Singapore, Singapore, Singapore.; N.1 Institute for Health, Institute for Digital Medicine, National University of Singapore, Singapore, Singapore.; Integrative Sciences and Engineering Programme, National University of Singapore, Singapore, Singapore.; Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA., Barch DM; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.; Department of Psychological and Brain Sciences, Washington University in St Louis, St Louis, MO, USA., Luna B; Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA., Fair DA; Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA. faird@umn.edu.; Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA. faird@umn.edu.; Institute of Child Development, University of Minnesota Medical School, Minneapolis, MN, USA. faird@umn.edu., Dosenbach NUF; Department of Neurology, Washington University School of Medicine, St Louis, MO, USA. ndosenbach@wustl.edu.; Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, USA. ndosenbach@wustl.edu.; Department of Radiology, Washington University School of Medicine, St Louis, MO, USA. ndosenbach@wustl.edu.; Program in Occupational Therapy, Washington University School of Medicine, St Louis, MO, USA. ndosenbach@wustl.edu.; Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA. ndosenbach@wustl.edu. |
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Jazyk: | angličtina |
Zdroj: | Nature [Nature] 2022 Mar; Vol. 603 (7902), pp. 654-660. Date of Electronic Publication: 2022 Mar 16. |
DOI: | 10.1038/s41586-022-04492-9 |
Abstrakt: | 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. (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.) |
Databáze: | MEDLINE |
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