Scientists discovered that multiple sclerosis (MS) develops when several risk factors work together through a shared biological pathway. The study found that having a past infection with Epstein-Barr virus, low vitamin D levels, limited sun exposure, and a specific genetic variant all increase MS risk—and they do this by changing how genes are turned on and off in your cells. Researchers studied over 800 people and found that these four different risk factors actually work through the same molecular switches, explaining why some people develop MS while others don’t. This discovery could help doctors better understand who’s at risk and potentially develop new prevention strategies.

The Quick Take

  • What they studied: Whether four known MS risk factors (past Epstein-Barr virus infection, low vitamin D, little sun exposure, and a specific gene variant) work together through the same biological mechanism to cause multiple sclerosis
  • Who participated: 833 total people across two studies: 206 people with MS and 348 without MS from Australia, plus 140 people with MS and 139 without MS from Sweden. Researchers compared their blood samples and medical histories.
  • Key finding: All four risk factors—Epstein-Barr virus, vitamin D deficiency, low sun exposure, and the HLA-DRB1*1501 gene variant—appear to increase MS risk by changing how genes are activated in cells. These changes explained 21-53% of the increased MS risk from these factors.
  • What it means for you: This research suggests that MS develops when multiple factors combine rather than from any single cause. If you have some of these risk factors, maintaining healthy vitamin D levels and sun exposure might be particularly important. However, this is early-stage research, and you should discuss MS risk with your doctor if you have concerns.

The Research Details

Researchers compared two groups of people: those who had developed multiple sclerosis and those who hadn’t. They collected blood samples and examined the DNA from these samples using special technology that measures which genes are turned on or off. This type of measurement is called ‘DNA methylation’ and acts like a dimmer switch for genes. The study was conducted in two different countries (Australia and Sweden) to see if the results would be consistent across different populations. By studying two separate groups, the researchers could confirm their findings were reliable and not just a fluke from one study.

Understanding how different risk factors work together is crucial because MS doesn’t seem to have just one cause. By identifying the shared biological pathway these four factors use, scientists can better predict who might develop MS and potentially develop treatments that target this common mechanism. This approach is more realistic than studying each risk factor in isolation.

This study has several strengths: it examined two separate populations in different countries, used standardized laboratory measurements, and applied rigorous statistical methods to test whether the findings were real. The researchers also performed sensitivity analyses, which means they tested their results in different ways to make sure the conclusions held up. However, the study is observational rather than experimental, so it shows associations rather than proving direct cause-and-effect relationships.

What the Results Show

The research identified two specific patterns of gene activation changes (called ‘DNAm modules’) that appeared in both the Australian and Swedish study groups. These patterns mediated—or explained—between 21-53% of the increased MS risk from the four factors combined. This means that roughly one-quarter to one-half of how these risk factors increase MS risk works through these shared gene-switching mechanisms. The genes involved in these patterns overlapped significantly with genes that previous large genetic studies had identified as MS risk genes, suggesting the researchers were looking at biologically meaningful changes. When the researchers looked at the biological pathways affected by these gene changes, they found that 45% of the same pathways were affected in both study populations, indicating the findings are consistent across different groups.

The study confirmed that each of the four risk factors individually increases MS risk, but the real insight is that they work together. The researchers found that the gene variant HLA-DRB1*1501 and Epstein-Barr virus infection history were particularly strongly associated with MS. The vitamin D and sun exposure findings support previous research suggesting that vitamin D deficiency is an important MS risk factor.

This research builds on decades of work showing that MS has multiple risk factors. Previous studies identified each of these four factors separately, but this is one of the first to show they may work through shared biological mechanisms. The findings align with the ‘multiple hits’ theory of MS, which suggests the disease requires several different factors to come together. The emphasis on epigenetic changes (how genes are regulated rather than changes to the DNA sequence itself) is a newer approach that’s gaining importance in understanding complex diseases.

The study is observational, meaning researchers observed associations but cannot prove these factors directly cause MS. The blood samples were taken after MS diagnosis in most cases, so the gene changes might be a result of MS rather than a cause. The study included relatively modest sample sizes, though the consistency across two populations strengthens confidence. The research doesn’t explain why these specific gene changes occur or how they lead to MS development. Additionally, the study primarily included people of European ancestry, so findings may not apply equally to other populations.

The Bottom Line

Based on this research (moderate confidence level): Maintain adequate vitamin D levels through diet, supplementation, or appropriate sun exposure, especially if you have other MS risk factors. Get regular sun exposure when safe and practical. If you have a personal or family history of MS, discuss these risk factors with your healthcare provider. This research does not yet support any specific new treatments, but it may guide future drug development.

This research is most relevant to people with a family history of MS, those who have had Epstein-Barr virus infection, and people living in areas with limited sun exposure. Healthcare providers and MS researchers should pay attention to these findings. People without MS risk factors can still benefit from maintaining healthy vitamin D levels and sun exposure for overall health, but they don’t need to take special action based solely on this study.

If you implement vitamin D and sun exposure recommendations, you might see improvements in vitamin D blood levels within 4-8 weeks. However, this research doesn’t indicate how quickly these changes might reduce MS risk, as MS develops over years or decades. Long-term monitoring would be needed to assess any protective effects.

Want to Apply This Research?

  • Track weekly sun exposure minutes (aim for 10-30 minutes most days) and vitamin D supplementation or dietary intake. Log any changes in energy levels or mood, as these may correlate with vitamin D status.
  • Set a daily reminder to spend 15-20 minutes outdoors during midday hours when UV exposure is most effective for vitamin D production. If supplementing, take vitamin D with a meal containing fat for better absorption.
  • Check vitamin D blood levels every 3-6 months through your healthcare provider. Track sun exposure and supplementation consistency weekly. Monitor for any new symptoms and maintain a log to discuss with your doctor at annual checkups.

This research is preliminary and observational in nature. It shows associations between risk factors and MS but does not prove direct causation. The findings are based on laboratory measurements and should not be used for self-diagnosis. If you have concerns about MS risk, family history of MS, or symptoms suggestive of MS (such as vision problems, numbness, or fatigue), consult with a neurologist or your primary care physician. Do not make changes to vitamin D supplementation or sun exposure habits without discussing with your healthcare provider, especially if you have other medical conditions or take medications. This information is for educational purposes and should not replace professional medical advice.