Power and optimal study design in iPSC-based brain disease modelling

Autor: Jessie W. Brunner, Hanna C. A. Lammertse, Annemiek A. van Berkel, Frank Koopmans, Ka Wan Li, August B. Smit, Ruud F. Toonen, Matthijs Verhage, Sophie van der Sluis
Přispěvatelé: Medical oncology laboratory, Human genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Functional Genomics, Molecular and Cellular Neurobiology, AIMMS, Amsterdam Neuroscience - Neurodegeneration, Center for Neurogenomics and Cognitive Research, Complex Trait Genetics
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecular Psychiatry. Nature Publishing Group
Molecular Psychiatry, 28(4), 1-12. Nature Publishing Group
Brunner, J W, Lammertse, H C A, van Berkel, A A, Koopmans, F, Li, K W, Smit, A B, Toonen, R F, Verhage, M & van der Sluis, S 2022, ' Power and optimal study design in iPSC-based brain disease modelling ', Molecular Psychiatry . https://doi.org/10.1038/s41380-022-01866-3
Brunner, J W, Lammertse, H C A, van Berkel, A A, Koopmans, F, Li, K W, Smit, A B, Toonen, R F, Verhage, M & van der Sluis, S 2022, ' Power and optimal study design in iPSC-based brain disease modelling ', Molecular Psychiatry, vol. 28, no. 4, pp. 1-12 . https://doi.org/10.1038/s41380-022-01866-3
ISSN: 1359-4184
DOI: 10.1038/s41380-022-01866-3
Popis: Studies using induced pluripotent stem cells (iPSCs) are gaining momentum in brain disorder modelling, but optimal study designs are poorly defined. Here, we compare commonly used designs and statistical analysis for different research aims. Furthermore, we generated immunocytochemical, electrophysiological, and proteomic data from iPSC-derived neurons of five healthy subjects, analysed data variation and conducted power simulations. These analyses show that published case–control iPSC studies are generally underpowered. Designs using isogenic iPSC lines typically have higher power than case–control designs, but generalization of conclusions is limited. We show that, for the realistic settings used in this study, a multiple isogenic pair design increases absolute power up to 60% or requires up to 5-fold fewer lines. A free web tool is presented to explore the power of different study designs, using any (pilot) data.
Databáze: OpenAIRE
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