Susceptibility Genes and Epigenetics in Sporadic ALS

The etiology of sporadic ALS (sALS) remains unclear; however, a number of candidate causal pathways are emerging. Evidence suggests that sALS patients carry susceptibility genes, and sALS is now understood to be a complex neurodegenerative disease in which gene‐environment interactions remain a possible cause. In this view, susceptibility genes confer risk, and environmental factors trigger disease onset. Another possible gene‐environmental basis of disease is environmental modifications to the epigenome. Here we discuss evidence implicating environmental factors in sALS, genetic susceptibility, and mounting evidence for candidate susceptibility genes. Finally, we discuss how environmental factors may alter the epigenome through in utero and post utero exposures in sALS and highlight key questions in the field.