New genetic associations found for restless legs syndrome

In the largest study of its kind, an international team of researchers identified new genetic variants associated with restless legs syndrome.

Published in the journal Lancet Neurology, the study also identified underlying biological pathways for the condition pointing researchers to possible drug targets for treatment.

“Restless legs syndrome is surprisingly common, but despite this, we know little about what causes it – and hence how to treat it,” said Dr. Steven Bell from the Department of Public Health and Primary Care at the University of Cambridge, and one of the lead authors of the study.

Characterized by an unpleasant urge to move the legs usually during inactivity, the condition is chronic and can disrupt sleep and impact a person’s long-term wellbeing. It affects as many as 10 percent of the people with European ancestry, and, according to researchers, it can lead to an increased risk for depression, anxiety, hypertension, and cardiovascular disease.

Although past studies identified a strong genetic link to the condition, this study, the largest conducted so far, identified 13 genetic variants newly associated with the condition and replicated six other previously identified associations. This study was far larger than previous genome wide association studies into the condition, using data from more than 110,000 people who were part of three different study groups, more than half of those were 23andMe customers who consented to participate in research. The findings were then replicated in a separate data set.

The new genetic variants identified in this study are on or near genes involved in changes in the formation of neuronal circuits as well as the growth and development of nerve cells, a process known as as neurogenesis.

“We are convinced that the newly discovered risk loci will contribute substantially to our understanding of the causal biology of the disease,” said Dr. Barbara Schormair, of the Institute of Neurogenomics at the Helmholtz Zentrum München, who co-authored the paper.

The researchers also noted that the drug thalidomide targets the interaction of one genes, MEIS2, which is involved in this process. Thalidomide, a sedative developed in Germany in the 1950s, was implicated in severe birth defects. No longer prescribed to women in childbearing years, and only approved by the FDA under what is called Risk Evaluation and Mitigation Strategies, the drug is currently used to treat multiple myeloma.

“The genetic risk variants that we’ve discovered add more weight to the idea that this condition is related to the development of our nervous system,” said Dr. Emanuele Di Angelantonio, another researcher on this study from the University of Cambridge. “It also gives us some clues to how we may treat patients affected by the condition.”

Find the full study at Lancet Neurology.