TY - JOUR
T1 - Power and optimal study design in iPSC-based brain disease modelling
AU - Brunner, Jessie W
AU - Lammertse, Hanna C A
AU - van Berkel, Annemiek A
AU - Koopmans, Frank
AU - Li, Ka Wan
AU - Smit, August B
AU - Toonen, Ruud F
AU - Verhage, Matthijs
AU - van der Sluis, Sophie
N1 - © 2022. The Author(s).
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85141990329&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41380-022-01866-3
DO - https://doi.org/10.1038/s41380-022-01866-3
M3 - Article
C2 - 36385170
SN - 1359-4184
VL - 28
SP - 1
EP - 12
JO - Molecular psychiatry
JF - Molecular psychiatry
IS - 4
ER -