Abstract
Human Genomics Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease with a genetic and environmental interaction. Lou Gehrig was a renowned professional American baseball player whose career was cut short by ALS, which has now also become known as Lou Gehrig's disease. Using Mendelian randomization (MR), which can help to identify genetic factors linked to phenotype, Julian et al. looked for genetic differences between individuals within the UK Biobank correlated with their activity level, including strenuous activity. From this, they identified genetic variants associated with ALS risk in individuals who regularly performed strenuous exercise. Of the validated ALS risk genes, 52% showed differential gene expression during exercise in individuals with such variants. Strenuous exercise is a highly heterogenous environmental factor, and more study is needed to determine how it becomes a risk factor for ALS. EBioMedicine 68 , 103397 (2021).
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