Genetic Study Shows No Solid Connection between ALS and Autoimmune Disorders

Celiac.com 05/08/2023 - A number of epidemiological studies have suggested a potential association between amyotrophic lateral sclerosis (ALS) and autoimmune disorders such as celiac disease, which are conditions where the immune system mistakenly attacks the body's own cells and tissues. 

To investigate whether there is an actual causal relationship between autoimmune disorders and ALS, a team of researchers conducted a study using Mendelian randomization to examine a  potential causal relationship between autoimmune disorders and ALS risk. 

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The research team included Paria Alipour, Konstantin Senkevich, Jay P. Ross, Dan Spiegelman, Despoina Manousaki, Patrick A. Dion, and Guy A. Rouleau. They are variously affiliated with the Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada; the Department of Human Genetics, McGill University, Montréal, QC, Canada; and the Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.

The researchers obtained data from large European genome-wide association studies (GWAS) on autoimmune disorders and used summary statistics to perform a two-sample Mendelian randomization analysis and then identified specific genetic markers, known as single nucleotide polymorphisms (SNPs), that were strongly associated with 12 different autoimmune disorders. They examined the effects of these SNPs on the risk of developing ALS using data from a large European ALS GWAS, which included over 27,000 ALS cases and more than 110,000 controls.

To ensure the accuracy of their analysis, the team excluded SNPs within a specific region called the human leukocyte antigen (HLA) region, which is known to have a complex genetic structure that could introduce biases.

Using statistical methods, the team computed inverse-variance weighted MR estimates and conducted sensitivity analyses to account for potential confounding factors. They also performed a reverse MR analysis to investigate whether ALS had any causal effects on the autoimmune disorders.

After adjusting for multiple testing, the Mendelian randomization analyses did not show a significant association between liability to autoimmune disorders and ALS risk. Similarly, the reverse Mendelian randomization analysis did not find evidence of ALS being a causal trigger for the autoimmune disorders examined.

Overall, this randomization study suggests that there is no direct causal relationship between liability to autoimmune disorders and ALS risk in the European population. 

The associations observed in previous epidemiological studies may be influenced by shared biological factors or environmental confounders that were not accounted for in this study. More research is needed to better understand the underlying mechanisms and potential connections between ALS and autoimmune conditions, but for now the evidence doesn't show any causal link.

Read more in BMC Medicine volume 20, Article number: 382 (2022)