Multidimensional reduction of multicentric cohort heterogeneity: An alternative method to increase statistical power and robustness.
Modern clinical research takes advantage of multicentric cohorts to increase sample size and gain in statistical power. However, combining individuals from different recruitment centers provides heterogeneity in the dataset that needs to be accounted for to obtain robust results. Sophisticated statistical multivariate models adjusting for center effect can be implemented, but they can become unstable and can be complex to interpret with the increasing number of covariates to consider. Here, we present a multidimensional reduction technique to identify heterogeneity in a French multicentric cohort of hematopoietic stem cell transplantations and characterize a homogeneous subgroup prior to performing simple statistical univariate analyses. The exclusion of outliers allowed the identification of two genetic factors associated with post-transplantation overall survival. We therefore provide proof-of-concept that a sample size reduction method can efficiently account for heterogeneity and center effect in multicentric cohorts while increasing statistical power and robustness for discovery of new association signals.
Methodomics, Toulouse, France.
Caroline
C
Le Gall
Methodomics, Toulouse, France.
Julie
J
Laurent
Laboratory of Experimental Immunology, Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Nicolas
N
Vince
Department of Neurology, University of California, San Francisco, CA, USA.
Antoine
A
Lizee
Department of Neurology, University of California, San Francisco, CA, USA.
Alisha
A
Agrawal
Etablissement français du Sang, Nantes, France; Inserm Unit 1064, Hospital and University of Nantes, Nantes, France.
Alexandre
A
Walencik
Etablissement français du Sang, Nantes, France.
Pauline
P
Rettman
Etablissement français du Sang, Nantes, France.
Katia
K
Gagne
Etablissement français du Sang, Nantes, France.
Christelle
C
Retiere
Department of Neurology, University of California, San Francisco, CA, USA.
Jill
J
Hollenbach
Etablissement français du Sang, Nantes, France.
Anne
A
Cesbron
Molecular Genetic Epidemiology Section, Basic Research Laboratory, Basic Science Program, NCI/NIH, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD, USA.
Sophie
S
Limou
Methodomics, Toulouse, France; Department of Neurology, University of California, San Francisco, CA, USA; Etablissement français du Sang, Nantes, France. Electronic address: pierre-antoine.gourraud@univ-nantes.fr.
Pierre-Antoine
PA
Gourraud
D000328:Adult; D015331:Cohort Studies; D005260:Female; D005602:France; D018740:Genetic Heterogeneity; D006085:Graft Survival / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D018401:Sample Size; D016019:Survival Analysis; D055815:Young Adult
Hematopoietic stem cell transplantation; Heterogeneity; Multicentric cohort; Multidimensional reduction; Multiple correspondence analyses