Unraveling the complex interplay between genes, environment, and climate in ALS.

Various genetic and environmental risk factors have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Despite this, the cause of most ALS cases remains obscure. In this review, we describe the current evidence implicating genetic and environmental factors in motor neuron degeneration. While the risk exerted by many environmental factors may appear small, their effect could be magnified by the presence of a genetic predisposition. We postulate that gene-environment interactions account for at least a portion of the unknown etiology in ALS. Climate underlies multiple environmental factors, some of which have been implied in ALS etiology, and the impact of global temperature increase on the gene-environment interactions should be carefully monitored. We describe the main concepts underlying such interactions. Although a lack of large cohorts with detailed genetic and environmental information hampers the search for gene-environment interactions, newer algorithms and machine learning approaches offer an opportunity to break this stalemate. Understanding how genetic and environmental factors interact to cause ALS may ultimately pave the way towards precision medicine becoming an integral part of ALS care.

Informations de copyright

Copyright © 2021. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Rosario Vasta and Ruth Chia declare no conflicts of interests. Bryan J. Traynor holds the US, Canadian and European patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion in C9orf72. He is an associate editor of Brain and sits on the editorial boards of Neurobiology of Aging, the Journal of Neurology, Neurosurgery, and Psychiatry, and EClinicalMedicine. Adriano Chiò serves on the editorial advisory board of Amyotrophic Lateral Sclerosis and Neurological Sciences and has received research support from the Italian Ministry of Health (Ricerca Finalizzata), Regione Piemonte (Ricerca Finalizzata), University of Turin and the European Commission (Health Seventh Framework Programme) and serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Denali Pharma, Cytokinetics, Biogen, and Amylyx and has a research contract with Biogen.