Project Y: The search for clues explaining phenotype variability in MS

Abstract Background To study phenotypic variability in MS patients, well-defined unbiased cohort studies are necessary. The most common and probably most important confounding factor when studying disease phenotype in MS is age. Objective To describe study design and subject characteristics of a unique birth cohort (Project Y). The overall aim of Project Y is to identify determinants associated with phenotypic variability in MS, eliminating the possibility of confounding by age. Methods Project Y is a population-based cross-sectional study of all people with MS born in the Netherlands in 1966. Patients and healthy controls were subjected to comprehensive examinations: functional and static imaging, physical and cognitive measurements, and lifestyle factors early and later in life. In addition body fluids were collected and stored for future biomarker research. Results 452 eligible MS patients were identified. Between December 2017 and January 2021, 367 MS patients and 125 healthy controls participated. The total number of identified cases results in a current prevalence of at least 189/100.000 for people born in the year 1966 in The Netherlands. Conclusion Project Y is a unique cohort designed to identify factors associated with phenotypic variability in MS patients without the confounding effects of age. This first description of the Project Y cohort indicates that the prevalence of MS in the Netherlands might be higher than previously presumed. Various studies using Project Y data are ongoing and results will be published in upcoming years.