ALS and MS May Be Influenced by Environmental Factors

By Irene Yeh

While ALS and MS have different prognoses and pathological markers, they are both incurable neurodegenerative diseases that have devastating impacts on both patients and families—and they are both of unknown etiology. Melissa Schilling, professor at New York University’s Stern School of Business, analyzed the distribution of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) in the U.S. using mortality data, and she found a significant geographic association of the mortality crude rates, even while controlling for race, gender, latitude, and access to neurological care and resources.

The mortality data were taken from death certificates from the U.S. Centers for Disease Control WONDER database, as well as mortality and demographic data from the World Health Organization (WHO). The results showed that the mortality crude rate for ALS was higher in men than women, and the rate for MS was higher in women than men. When the men and women groups were kept separate, there was a strong positive correlation of more than 70% in the geographic distribution of ALS and MS. Additionally, the crude mortality rates for ALS and MS were significantly higher for white patients with a significant portion of white patients being of Hispanic origin in the U.S. The diseases were also more common among Black patients than Asian.

But when the men and women groups were pooled together, it revealed a Simpson’s paradox, a statistical phenomenon where a trend appears in different groups of data but disappears or reverses when the groups are combined. The obscuration in this study occurred due to ALS being more common in men and MS being more common in women. Schilling, who specializes in analyzing large-scale datasets via econometrics, believes this paradox is the reason why the relationship between these two diseases has been overlooked.

Schilling explains in a press release that the results were surprising because “previous studies have typically concluded there was no evidence for a mechanistic or genetic link between the two diseases.”

It was thought that MS had a correlation with latitude. For decades, researchers noticed a north-south gradient distribution of MS in the U.S. and speculated that UV light or vitamin D may be a factor in the disease. However, studies that supplemented patients with UV light or vitamin D did not show any significant results.

Using the mortality data from the U.S. and WHO databases showed that ALS and MS have a strong geographic relationship with each other, even after controlling latitude, race, gender, and economic factors. This indicates that ALS has at least as strong of a geographic pattern as MS and that the two diseases have a link that has yet to be explored and understood.

“I was very surprised to find such a strong geographic pattern as most of the research on ALS does not emphasize the role of geography,” says Schilling. “I was even more surprised to find that ALS has a very strong association with the geography of MS.”

Schilling brings up a few explanations for this relationship. ALS and MS may have a genetic link that is difficult to detect. However, in order for this explanation to hold up, there would also be a north-south gradient distribution of the genotype or the discovery of an epigenetic interaction with some external environmental element (Scientific Reports, DOI: 10.1038/s41598-025-18755-8).

This brings about the possibility of an environmental factor affecting the two diseases. Investigating environmental elements can provide clues to determine how they could be treated, as well as what causes them and how to avoid them. Environmental elements include viruses, parasites, algae, and mold, as well as human-made elements such as industrial practices, agricultural practices, and more. Further research would be required to explore this possibility.

Schilling also highlights a third explanation. There could have been a systematic error in the data. The rate of misdiagnosis of ALS and MS is unknown, despite experts considering it a rare occurrence. In order to ascertain if there were data errors, then these results need to be compared with a geographically-stratified sample where ALS and MS diagnoses were obtained in a precise and standardized way.

It must also be mentioned that the study did have limitations. First, ALS and MS are difficult to accurately diagnose. When introducing multinational variance into an analysis of these diseases, it likely amplifies those measurement problems. Secondly, the racial differences in the mortality crude rates were significant, and the race indicators are not provided in the World Health Organization (WHO) mortality data. Third, there is a lack of standardization between U.S. death certificates and WHO’s database, which could indicate unreliability in the data sources.

While the study did not pinpoint an exact cause, it provided direction for further research to discover the causes of ALS and MS and how to properly treat—as well as avoid—the diseases.