A large international team of scientists has uncovered genetic risk factors for multiple system atrophy, a disease that was previously thought to have no genetic explanation, according to a study published in Neuron.
Multiple system atrophy (MSA) is a rare, progressive disease affecting the brain and nervous system which causes movement dysfunction, muscle pain and difficulty swallowing. The average survival rate from the time symptoms appear is six to 10 years, according to the National Institutes of Health.
Prior to this development, MSA was thought to be sporadic, meaning the disease had no known genetic explanation, said Steven Lubbe, PhD, assistant professor in the Ken and Ruth Davee Department of Neurology’s Division of Movement Disorders and a co-author of the study.
“This study represents a huge milestone for the field of MSA,” Lubbe said. “This is one of the largest studies looking at the genetics of MSA and it’s also the first study that’s comprehensive in its approach to try and identify genetic factors linked to the disease.”
In the study, a team of investigators from around the world performed whole genome sequencing on 888 European-ancestry MSA cases and 7,128 controls. They identified four loci –locations on the genome – that were significantly associated with developing MSA.
By analyzing the RNA from the study participants, the investigators found that people with mutations in genes USP38-DT, KCTD7 and lnc-KCTD7-2 were more susceptible to developing MSA, according to the study.
“While previously, people thought there might not be any genetics involved in MSA. We’ve now shown that there are in fact both common and rare variants influencing whether or not a person gets MSA,” Lubbe said. “Finally, the door is opened to uncovering additional genetic factors for MSA.”
All data gathered from the study will be made available to the scientific community, Lubbe said, with the hopes that other investigators can add to the data to uncover more genetic associations with MSA. Moving forward, more work is also needed to understand the genomes of people with MSA who come from non-European backgrounds, he said.
“The next step here is to try and get more samples to build on what we’ve just uncovered, and an important next step is to move away from the European population, which the study is mainly based on, into other understudied population groups,” Lubbe said.
The study also represents a win for scientific collaboration, Lubbe said, as investigators from around the world helped to supply genomic information for the rare disease.
“It’s just the tip of the iceberg of what is going to come in terms of MSA genetics,” Lubbe said.
The study was supported by National Institute on Aging grant RF1 AG057474 and U01 AG061356. The study was also supported by the NUgene Project, which identified MSA patient samples.
