A study of more than 22,000 people with multiple sclerosis (MS) has for the first time identified a genetic variant associated with faster progression of the disease, an accumulation of disability that can rob patients of their mobility and independence over time.
Multiple sclerosis begins as an autoimmune disease where the immune system attacks the brain and the spinal cord, resulting in symptom flares, called relapses, as well as longer-term degeneration known as progression.
Despite the development of effective treatments for the inflammatory autoimmune disease, none can prevent increased disability during the neurodegenerative phase of the disease.
The new study, which includes researchers from Yale and was published in Nature on June 28, is the first to identify a genetic variant that increases disease severity, an advance that the authors say offers a key step toward understanding and eventually fighting this progressive form of MS.
“While we have identified genetic variants that are predominantly immune related associated with risk of developing MS, this is the first study to identify neuronal genetic variants associated with the neurodegenerative aspects of the disease,” said Dr. David Hafler, the William S. and Lois Stiles Edgerly Professor of Neurology and Professor of Immunobiology at Yale School of Medicine, chair of the Department of Neurology, and an author of the study.
The work was the result of a large international collaboration of the International MS Genetics Consortium (IMSGC), which consists of more than 70 institutions from around the world. Hafler is a co-founder of the IMSGC.
Previous studies have shown that MS susceptibility, or risk, stems in large part from dysfunction in the immune system. Some of this dysfunction can be treated, slowing the progression of the disease.
But “these risk factors don’t explain why, 10 years after diagnosis, some MS patients are in wheelchairs while others continue to run marathons,” said Sergio Baranzini, a professor of neurology at University of California, San Francisco and co-senior author of the study.
For the first part of the new study, researchers combined data from more than 12,000 people with MS to complete a genome-wide association study (GWAS), a research approach that uses statistics to carefully link genetic variants to particular traits. In this case, the traits of interest were related to MS severity, including the years it took for each individual to advance from diagnosis to a certain level of disability.
After sifting through more than 7 million genetic variants, the scientists found one that was associated with faster disease progression. The variant sits between two genes with no prior connection to MS, called DYSF and ZNF638.
They found that MS patients with two copies of the gene variant, located near the two genes that help repair damaged cells and one that helps control viral infection, experienced faster disease progression. The location of the variant suggests a possible mechanism for accelerated progression.
“Inheriting this genetic variant from both parents accelerates the time to needing a walking aid by almost four years,” Baranzini said.
“These genes are normally active within the brain and spinal cord, rather than the immune system,” said Adil Harroud, assistant professor of neurology at the Montreal Neurological Institute and lead author of the study.
“Our findings suggest that resilience and repair in the nervous system determine the course of MS progression and that we should focus on these parts of human biology for better therapies.”
The findings give the field its first significant leads to address the nervous system component of MS.
To confirm their findings, the scientists investigated the genetics of nearly 10,000 additional MS patients. Again, they found that those with two copies of the variant became disabled faster.
“This gives us a new opportunity to develop new drugs that may help preserve the health of all who suffer from MS,” Harroud said.
This work was supported in part by funding from the National Institute of Neurological Disorders and Stroke (which is part of the National Institutes of Health), the European Union’s Horizon 2020 Research and Innovation Funding Programme, and the Multiple Sclerosis Society of Canada.
Hafler is a Yale Cancer Center member in the Yale Cancer Immunology Research Program.

News
New Once-a-Week Shot Promises Life-Changing Relief for Parkinson’s Patients
A once-a-week shot from Australian scientists could spare people with Parkinson’s the grind of taking pills several times a day. The tiny, biodegradable gel sits under the skin and releases steady doses of two [...]
Weekly injectable drug offers hope for Parkinson’s patients
A new weekly injectable drug could transform the lives of more than eight million people living with Parkinson's disease, potentially replacing the need for multiple daily tablets. Scientists from the University of South Australia [...]
Most Plastic in the Ocean Is Invisible—And Deadly
Nanoplastics—particles smaller than a human hair—can pass through cell walls and enter the food web. New research suggest 27 million metric tons of nanoplastics are spread across just the top layer of the North [...]
Repurposed drugs could calm the immune system’s response to nanomedicine
An international study led by researchers at the University of Colorado Anschutz Medical Campus has identified a promising strategy to enhance the safety of nanomedicines, advanced therapies often used in cancer and vaccine treatments, [...]
Nano-Enhanced Hydrogel Strategies for Cartilage Repair
A recent article in Engineering describes the development of a protein-based nanocomposite hydrogel designed to deliver two therapeutic agents—dexamethasone (Dex) and kartogenin (KGN)—to support cartilage repair. The hydrogel is engineered to modulate immune responses and promote [...]
New Cancer Drug Blocks Tumors Without Debilitating Side Effects
A new drug targets RAS-PI3Kα pathways without harmful side effects. It was developed using high-performance computing and AI. A new cancer drug candidate, developed through a collaboration between Lawrence Livermore National Laboratory (LLNL), BridgeBio Oncology [...]
Scientists Are Pretty Close to Replicating the First Thing That Ever Lived
For 400 million years, a leading hypothesis claims, Earth was an “RNA World,” meaning that life must’ve first replicated from RNA before the arrival of proteins and DNA. Unfortunately, scientists have failed to find [...]
Why ‘Peniaphobia’ Is Exploding Among Young People (And Why We Should Be Concerned)
An insidious illness is taking hold among a growing proportion of young people. Little known to the general public, peniaphobia—the fear of becoming poor—is gaining ground among teens and young adults. Discover the causes [...]
Team finds flawed data in recent study relevant to coronavirus antiviral development
The COVID pandemic illustrated how urgently we need antiviral medications capable of treating coronavirus infections. To aid this effort, researchers quickly homed in on part of SARS-CoV-2's molecular structure known as the NiRAN domain—an [...]
Drug-Coated Neural Implants Reduce Immune Rejection
Summary: A new study shows that coating neural prosthetic implants with the anti-inflammatory drug dexamethasone helps reduce the body’s immune response and scar tissue formation. This strategy enhances the long-term performance and stability of electrodes [...]
Scientists discover cancer-fighting bacteria that ‘soak up’ forever chemicals in the body
A family of healthy bacteria may help 'soak up' toxic forever chemicals in the body, warding off their cancerous effects. Forever chemicals, also known as PFAS (per- and polyfluoroalkyl substances), are toxic chemicals that [...]
Johns Hopkins Researchers Uncover a New Way To Kill Cancer Cells
A new study reveals that blocking ribosomal RNA production rewires cancer cell behavior and could help treat genetically unstable tumors. Researchers at the Johns Hopkins Kimmel Cancer Center and the Department of Radiation Oncology and Molecular [...]
AI matches doctors in mapping lung tumors for radiation therapy
In radiation therapy, precision can save lives. Oncologists must carefully map the size and location of a tumor before delivering high-dose radiation to destroy cancer cells while sparing healthy tissue. But this process, called [...]
Scientists Finally “See” Key Protein That Controls Inflammation
Researchers used advanced microscopy to uncover important protein structures. For the first time, two important protein structures in the human body are being visualized, thanks in part to cutting-edge technology at the University of [...]
AI tool detects 9 types of dementia from a single brain scan
Mayo Clinic researchers have developed a new artificial intelligence (AI) tool that helps clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using a single, widely available scan—a transformative [...]
Is plastic packaging putting more than just food on your plate?
New research reveals that common food packaging and utensils can shed microscopic plastics into our food, prompting urgent calls for stricter testing and updated regulations to protect public health. Beyond microplastics: The analysis intentionally [...]