Research Question:
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Currently, the pathogenesis of ALS remains unclear, and its incidence is higher among males, middle-aged and elderly individuals, and those engaged in heavy physical labor. Treatment options for ALS are limited, and there is no cure. Therefore, exploring modifiable risk factors to reduce the incidence of ALS is an important approach to alleviating the disease burden.
Objectives:
This study aims to comprehensively identify modifiable risk factors for ALS through an exposome-wide association study (EWAS). Additionally, a composite risk score will be developed based on these risk factors to evaluate the benefits of preventing them.
Scientific Rationale for the Research:
EWAS is a hypothesis-free strategy that systematically and agnostically examines the relationships between multiple variables and a single outcome. This technique has been successfully applied to various complex diseases, including depression, HIV/AIDS, and diabetes. EWAS validates established factors from previous studies, reduces bias and false-positive results, and has the potential to uncover novel risk factors. The analytical rationale is similar to that of genome-wide association studies (GWAS), employing standardized analytical procedures to produce more robust results compared to hypothesis-driven approaches. Furthermore, by constructing composite risk scores and calculating population attributable fractions (PAF), the joint effects of multiple risk factors can be combined, and their contribution to ALS prevalence can be determined.