London – A new study identifying previously unrecognized genes associated with amyotrophic lateral sclerosis (ALS) has been published in Nature Genetics.
ALS can have a genetic component, and in many cases the risk of developing the disease is believed to be influenced by rare genetic variants, often with incomplete penetrance.
To investigate these variants, researchers analyzed one of the largest exome-sequencing datasets currently available, including 13,138 ALS patients and 69,775 controls, followed by a replication analysis involving 4,781 patients and 130,928 controls.
The study is the result of collaboration among numerous international research groups and included contributions from Vincenzo Silani, professor at the University of Milan and Director of the Department/Laboratory of Neurosciences at IRCCS Istituto Auxologico Italiano, and Nicola Ticozzi, Associate Professor of Neurology at the University of Milan and Head of the Neurology Unit at Auxologico, both affiliated with the Dino Ferrari Center.
“The joint analysis of data from 22 cohorts allowed us to obtain robust and comparable results,” Ticozzi explained. “The findings largely confirm existing knowledge on ALS genetics while also pointing to new genes potentially associated with the disease. In particular, the genes YKT6 and ARPP21 showed significant associations in both the discovery and replication phases. Other genes, including KNTC1, HTR3C, and GBGT1, are of interest but require further investigation.” Silani added: “The analysis also suggests a possible involvement of genes related to RNA splicing processes and identifies candidate genes such as CAPN2, UNC13C, KIF4A, and TTC3, which share features with genes already known to be implicated in ALS. These findings improve our understanding of the disease’s biological mechanisms, although they do not yet have direct clinical implications.” The study reinforces the view that ALS is a genetically complex disease in which multiple factors contribute to individual risk. Participation in large international collaborative studies such as this one is essential to advancing understanding of the disease and, in the long term, supporting the development of new diagnostic and therapeutic strategies.