High LDL cholesterol levels, also known as “bad cholesterol,” may contribute to the development of amyotrophic lateral sclerosis (ALS), researchers report.
Their study, “Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis” was published in Annals of Neurology.
Several lifestyle and other factors are thought to be associated with ALS. But, so far, the only established risk factors are older age, male gender, and a family history of the disorder.
To better clarify potential risk factors for ALS, researchers in the U.S. and U.K. looked into genetic datasets of nearly 25 million people (24.5 million from published genome-wide association studies and around 337,159 from the UK Biobank studies).
Of note, genome-wide association studies (GWAS) search the genome for small variations that occur more frequently in people with ALS, for instance, than in those without the disease. Such group distinctions help scientists identify genes that may raise a risk of developing this neurodegenerative disorder.
Researchers used analytical techniques to assess causality, and to examine the extent to which multiple genes involved in distinct diseases might also contribute to the risk of ALS.
More than 700 genetically observable traits were analyzed.
ALS was positively linked with smoking — including both passive and light smoking – and moderate levels of physical activity, which may be detrimental to motor neurons.
Interestingly, “traits related to light physical activity including walking for pleasure, walking as a mean of transport and light [‘do it yourself’] physical activities were associated with decreased risk of developing ALS,” the team reported.
Noting this complex relationship of ALS risk to exercise, the researchers added that their data offers no further insights into exercise, including “any insight into the effect of exercise on survival” once ALS symptoms are evident.
Higher cognitive performance and education levels also associated with a lower ALS risk, suggesting that genes controlling mental abilities may also be involved in ALS.
High LDL cholesterol levels were found to be a causal risk factor for this disease when investigators studied genetic markers of cholesterol levels in the datasets (they did not have direct information on cholesterol levels among individuals).
An increased risk of ALS due to coronary heart disease was also reported, but this was determined to be ultimately driven by high LDL cholesterol.
“We used genetic risk profiling to estimate the extent to which risk of developing ALS is attributable to LDL cholesterol,” the researchers wrote. “We found that individuals with the highest burden of genetic risk were 1.075 times more likely to develop ALS” and this rise in risk “associated with LDL cholesterol levels was similar across different subtypes of ALS.”
They suggested that blood cholesterol-lowering medications like statins may reduce this risk, but controlled clinical trials are necessary to confirm this hypothesis.
“We have well-established drugs that can lower cholesterol and we should look into whether they could protect against this terrible disease, which currently has no cure,” Alastair Noyce, a clinical senior lecturer at Queen Mary University of London, said in a press release.
“The next steps will include studying whether lowering levels of cholesterol might have a protective effect against [ALS], and potentially evaluating the use of cholesterol-modifying drugs in people at risk of [ALS],” Noyce added.
As the study concluded: “Our data lead us to propose that lowering blood cholesterol levels is a viable strategy for reducing risk associated with ALS. A similar approach may be effective in Alzheimer’s disease where exposure to statins is associated with substantially reduced risk of dementia in observational studies.”
Its results were also published in a public online platform, which will be updated as new data becomes available, giving the opportunity for other research teams to explore ALS risk factors and shared disease mechanisms, with the goal of it becoming “a valuable tool for the ALS community,” the researchers wrote.
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