Study finds early-life events may be environmental risk factors for ALS
Growing up in rural areas, having younger parents may increase one's risk
People with amyotrophic lateral sclerosis (ALS) are more likely than those without the neurodegenerative disease to have grown up in rural areas, have younger parents, and have lower levels of education, a new study found.
These results suggest that events and conditions in early life may be potential environmental factors that increase a person’s risk of developing the disease, according to the study’s researchers, from The University of Sydney in Australia.
“Reducing exposure to adverse environmental factors in early life could help to lower the risk of later developing ALS,” the researchers wrote.
The team theorized that these early environmental factors may be the first step in a longer process in which the risk of developing ALS increases over time.
“Effect sizes were small for these statistically significant variables, consistent with the multistep hypothesis for ALS in which several factors, each with a modest adverse effect, accumulate until a disease-inducing tipping point is reached,” the researchers wrote.
The study, “Early life events may be the first steps on the multistep path to amyotrophic lateral sclerosis,” was published in the journal Scientific Reports.
Investigating the environmental factors that may influence ALS risk
A number of environmental and genetic factors are believed to influence the risk of developing ALS. These include mutations in known ALS-associated genes, epigenetic alterations that change how certain genes are read, and exposure to toxic substances or infectious agents.
No single factor is enough to cause a person to develop the disease. Some researchers believe that “multiple environmental insults, all with small cumulative effect sizes,” may be needed for ALS to develop — which makes it difficult to pinpoint individual risk factors and reduce exposure to them.
“Despite the challenges to finding all the genetic/epigenetic and environmental factors that underlie ALS, further research into this area of research is to be encouraged in an attempt to disrupt the chain of these events before they have a chance to trigger the disease,” the team wrote.
Building on links found in other adult-onset diseases, this duo from the university’s School of Medical Sciences put forward the hypothesis that early-life factors, such as where a person was born or how long they’ve studied, may be contributing environmental factors. To compare how such factors differ between people with and without ALS, they looked at the results of an online questionnaire on the disease.
That questionnaire, called ALS Quest, collected answers from 1,049 people worldwide, ages 40 or older — including 568 who reported having received a diagnosis of ALS. Nearly half of these patients first noticed weakness in their arms and legs. Other common early symptoms were slurred speech and muscle twitches. Another 481 respondents who answered no to having ALS served as controls.
Despite the challenges to finding all the genetic/epigenetic and environmental factors that underlie ALS, further research into this area of research is to be encouraged in an attempt to disrupt the chain of these events before they have a chance to trigger the disease.
Analyzes showed that the proportion of people with ALS who were born in a country area was higher than that of those born in a city area (45.7% vs. 36.7%). That translated into a 50% increase in the odds of developing the disease for those born in a country area. The odds of having ALS decreased from rural areas to suburbs and inner cities.
Living more years in the countryside was also linked to an increased risk of ALS. The data showed ALS patients spent a median of nine more years living in country areas than people without the disease (16 vs. 6 years).
“Rural living could lead to exposure to farm-related herbicides and pesticides, a reported risk factor for ALS,” the researchers wrote, adding that people living in the countryside may be more exposed “to the effects of seasonal changes such as increased humidity leading to infectious diseases that may be involved in ALS.”
Some early-life factors, such as whether parents smoked, not linked to ALS
Another finding was that ALS patients were more likely to have younger parents. Compared with people without ALS, those with the disease had both younger fathers (median age 30 vs. 32 years) and slightly younger mothers (median age 28 vs. 29 years).
Education levels also differed, with fewer patients having postgraduate degrees compared with people without ALS (18.5% vs. 26.6%). While the median years of education were the same — 16 years for each group — patients had fewer years of education overall. According to the researchers, this could give people with ALS different life opportunities and increased exposure to environmental factors at work.
Overall, the study showed that where people live and what level of education they achieve may be among the factors in later ALS development, according to the team.
“Key findings of this study are that people with ALS are more likely to have been born in a country area than in a city area, to have lived longer in a country area, to have younger parents, to have lower educational attainment, and to have had fewer years in education,” the researchers wrote.
Other early-life factors, such as how many siblings a person had, birth weight, and whether an individual’s parents smoked, were not linked to ALS in this study.
Nonetheless, the researchers concluded that “this study indicates that a range of early life events and conditions could represent initial steps in the multistep path to ALS.”
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