Genetic Factors

Health care professionals can identify a specific genetic mutation that strongly contributes to the development of ALS in approximately two out of three people with familial ALS (people with a family history of the disease) and about one out of 10 people with sporadic ALS (people with no family history of the disease). These mutations are most often found in the C9orf72, SOD1, FUS, and TARDBP genes, at least in people of European descent. 

Just because a person has an ALS-linked gene mutation does not automatically mean they will develop the disease. Some gene mutations cause such a significant change in cell function that anyone who has it is highly likely to develop ALS at some point. Examples of these include many of the mutations identified in the SOD1 and C9orf72 genes, as well as other less common mutations. Other gene mutations increase ALS risk, but the disease may not develop without the presence of other risk factors, such as those described below. 

For most people living with ALS, though, there are no clear genetic links to the disease. As our understanding of ALS has evolved, it is now thought that that a combination of things, including multiple genetic factors, environmental exposures, habits, and career choice, most likely contributes to the disease developing.

Understanding Risk

Before we talk about the impact of specific environmental and lifestyle factors, it’s important to understand what “increased risk” means for a rare disease like ALS. In the United States, approximately 30,000 people currently live with ALS, which means a person’s absolute risk of developing the disease during their lifetime (if they don’t have a family history) is very low—less than a 1% chance. So, when research identifies an environmental or lifestyle factor that is linked to a higher risk of developing ALS, it usually translates into a few extra people with that risk factor being diagnosed each year.

It can be easier to think about this in terms of money. Let’s say you go to Las Vegas, put money on red at the roulette wheel, and hit—winning twice what you bet. You will have gained a lot more if you bet $1 million than if you only bet $1. In both cases, you doubled your money, but the increase in actual dollars is quite different. So, with a rare disease like ALS, a specific factor might double the risk, but the absolute risk of developing the disease still remains low, like the $2 in winnings in our roulette example. 

Environmental and Lifestyle Factors 

Individual institutional and large-scale funded research efforts, like the National ALS Registry hosted by the Centers for Disease Control and Prevention (CDC), have identified a number of chemical, biological, or other agents in the environment and lifestyle habits that might increase ALS risk. Researchers pinpoint these potential risk factors by comparing the exposures, jobs, and habits of people who have developed ALS to people who have not.

It is extremely challenging, though, to identify the full range of factors that contribute to ALS risk. The first obstacle is that, as we said before, ALS is a rare disease. As a result, it is hard to recruit enough people willing to participate in environmental research to be able to make definitive conclusions. The second roadblock is the large number of things people are exposed to throughout their lifetimes, which makes it difficult to tease apart the individual contributions of these diverse factors to ALS risk.

Despite these challenges, researchers have identified several environmental and lifestyle factors that likely increase ALS risk. These include:

• Military service
• Exposure to environmental toxins
• Brain and spinal cord injuries
• Specific occupations
• Smoking

Military Service

Shortly after the 1990–1991 Persian Gulf War, a number of studies were conducted in response to reports that ALS was occurring in Gulf War veterans at an unexpectedly high rate, particularly among young veterans who had not yet reached the age when ALS usually develops. One such study examined nearly 2.5 million military personnel who were on active duty during the time of the Gulf War. The researchers found that those serving in the Gulf were nearly twice as likely to develop ALS as those not serving in the Gulf. They also found an increased risk of ALS among all branches of the military, although Army and Air Force personnel experienced the greatest risk.

This increased ALS risk has been observed in veterans of other wars as well, such as World War II, the Korean War, and the Vietnam War, including those who did not serve in combat. More recently, a 2019 study found that service members who were deployed to post-9/11 conflicts were diagnosed with ALS more often than veterans who served in the Gulf War.

Researchers have theorized that the higher risk of ALS among military service members could be caused by exposure to toxic substances or head injuries. However, more research is needed to figure out exactly what aspects of military service increase ALS risk. To learn more about ALS in the military, click here.

Environmental Toxins

Many research studies over the years have looked at the relationship between ALS and toxic substances in the environment, including: 

• Beta-methylamino-L-alanine (BMAA)
• Heavy metals, such as lead, manganese, mercury, zinc, and copper
• Pesticides, herbicides, and insecticides
• Solvents, such as benzene, formaldehyde, and methylene chloride

BMAA is the most-studied environmental factor associated with ALS. It was originally identified in cycad seeds in Guam after ALS became 50 to 100 times more common than expected in the native Chamorro people, whose traditional diet included these seeds, between 1940 and 1965. BMAA is also produced by some kinds of cyanobacteria, blue-green bacteria that typically are found in bodies of water. According to a 2022 review of 258 studies, there is a strong association between BMAA and ALS.

Scientists continue to investigate the possible links between other environmental toxins and ALS. For example, in 2024, using data from the National ALS Registry and Biorepository, researchers found exposure to five specific chemicals used in dyes, batteries, solvents, steel, and rubber increased the chances of developing ALS by three to six times. Other researchers are trying to determine if combinations of several environmental toxins may be more important than exposure to any one toxin alone.

Brain and Spinal Cord Injuries

For decades, trauma to the head, neck, or spine, and especially traumatic brain injuries, have been considered potential risk factors for developing ALS. In 2021, researchers analyzed 14 different studies on this topic and concluded that having any type of head injury could increase ALS risk. The risk was higher for people who experienced more severe head injuries. This may be one reason why people who have served in the military or played professional sports, especially professional football and soccer, have an increased risk of developing ALS.

Occupation

In addition to serving in the military and playing certain professional sports, studies have linked an increased risk of ALS to jobs in manufacturing, welding, chemical operations, painting, construction, and mining. Electricians, mechanics, and train drivers also may be at potentially higher risk of developing ALS.

Some of this increased risk could be due to exposure to metals, fine particles, volatile solvents, and combustion pollutants while on the job. Severe electric shocks and long-term exposure to low-frequency electromagnetic fields have also been flagged as potential contributing factors, but recent evidence does not support this association.

Smoking

There is conflicting evidence about whether smoking contributes to a person’s risk of developing ALS, although it is often considered a “probable” risk factor. Some research suggests that the risk of ALS is higher among people who currently or previously smoked cigarettes, compared to those who never smoked. Other studies have only found an association between current smoking and an increased ALS risk but not previous smoking. Still others have shown that smoking may be a risk factor for women, especially post-menopausal women, but not for men.

Moving from Risks to Prevention

Being able to identify risk factors and the people most at risk for ALS creates the opportunity to develop strategies to prevent the disease from ever occurring. Progress has already been made for those with an ALS-linked gene mutation. This includes the first-ever ALS prevention trial, which is testing the efficacy of the genetic therapy Qalsody (tofersen) in people with a SOD1 mutation who have not developed symptoms of ALS. Developing prevention strategies for ALS that does not have a known genetic cause has been more difficult and will require a greater understanding of all potential environmental exposures and work and lifestyle habits that increase disease risk.

To support efforts to identify and validate new risk factors, we worked with Congress to enact the ALS Registry Act and secured federal funding to design, build, and implement the National ALS Registry at the CDC’s Agency for Toxic Substances and Disease Registry. We now serve as a federal contractor to the CDC, supporting National ALS Registry promotion efforts and strategy through our network of care services, ALS Certified Centers and Clinics, and the ALS support community.

Since 2022, we have also funded research designed to translate identified risk factors into clinical prevention strategies. Through our Prevention Grants, we support the development of interventions or tools that could one day be used to prevent or delay the onset of ALS. Because of the urgent need to offer advice about reducing ALS risk to families affected by the disease, we focus on funding projects that could be implemented in clinics within the next five to seven years. This is a key step in reaching our goal of making ALS a livable disease.