ALS Researchers Identify Gene Variants that Appear to Influence Patient Survival

A multi-disciplinary team of researchers analyzed the genotype data of thousands of ALS patients, with the objective of identifying gene variants that influence survival in ALS. The genome-wide association study identified two novel loci that significantly influence patient survival. These key findings help researchers better understand the biology of the disease and the identification of possible therapeutic targets.

The research paper, “Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis,” was recently published in JAMA Neurology.

Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, is characterized by progressive muscle weakness and paralysis due to the loss of motor neurons in the brain and spinal cord. According to the National Institute of Neurological Disorders and Stroke, more than 12,000 people in the U.S. are diagnosed with ALS and a large proportion of people with ALS die from respiratory failure. Although the prognosis is not good, approximately 10 percent of people with ALS survive 10 or more years.

In this study, researchers conducted a genome-wide association study (GWAS), analyzing the survival data of 4,256 patients with ALS obtained in the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study included genotype data extended to 7, 174 ,392 gene variants.

The results indicate that, among the study population, two novel loci were significantly associated with ALS survival, at 10q23 (variation rs139550538) and in the CAMTA1 gene at 1p36 (variation rs2412208). For the first locus, researchers found that patients with the AA or AT genotype code had an eight-month reduction in survival compared with patients carrying the TT genotype. In the CAMTA1 gene locus, patients with the GG or GT genotype had a four-month reduction in survival compared with TT carriers.

“Identification of modifier genes that might influence ALS survival could improve the understanding of the biology of the disease and suggest biological targets for pharmaceutical intervention. In addition, genetic risk scores for survival could be used as an adjunct to clinical trials to account for the genetic contribution to survival,” the researchers wrote in the study’s conclusion.