Physical exercise is a risk factor for amyotrophic lateral sclerosis: Convergent evidence from Mendelian randomisation, transcriptomics and risk genotypes.

ABSTRACT:

Background

Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease. ALS is determined by gene-environment interactions and improved understanding of these interactions may lead to effective personalised medicine. The role of physical exercise in the development of ALS is currently controversial.

Methods

First, we dissected the exercise-ALS relationship in a series of two-sample Mendelian randomisation (MR) experiments. Next we tested for enrichment of ALS genetic risk within exercise-associated transcriptome changes. Finally, we applied a validated physical activity questionnaire in a small cohort of genetically selected ALS patients.

Findings

We present MR evidence supporting a causal relationship between genetic liability to frequent and

SUBMITTER: Julian TH 

PROVIDER: S-EPMC8170114 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature