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

• Published in: Molecular psychiatry Vol. 28; no. 4; pp. 1545 - 1556
• Main Authors: Brunner, Jessie W., Lammertse, Hanna C. A., van Berkel, Annemiek A., Koopmans, Frank, Li, Ka Wan, Smit, August B., Toonen, Ruud F., Verhage, Matthijs, van der Sluis, Sophie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2023; Nature Publishing Group
• Subjects: 13/100; 14/1; 14/19; 631/1647; 631/378; 631/532; 692/699; 82/58; 82/80; 9/74; Antibodies; Behavioral Sciences; Biological Psychology; Brain Diseases; Brain research; Case-Control Studies; Genetics; Genomics; Healthy Volunteers; Humans; Induced Pluripotent Stem Cells; Inhibitory postsynaptic potentials; Laboratory animals; Medicine; Medicine & Public Health; Morphology; Neurosciences; Peptides; Pharmacotherapy; Pluripotency; Proteomics; Psychiatry; Spectrum analysis; Statistical analysis; Statistical power; Stem cells
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/s41380-022-01866-3

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.