Genetics and stem cells

Study finds genetic link to restless legs

A genetic variation that makes it more likely for the carrier to suffer from restless leg syndrome has been identified, Metro reported. “This would mean the twitching is a biological and not a psychological disorder,” the newspaper said.

Restless leg syndrome is thought to affect 15% of the population and causes itching or twitiching of the legs, usually after the person has gone to bed; it can be relieved by moving the legs.

The researchers noted that the gene variant was associated with lower iron levels, as found in previous research.

This and other stories on the subject were based on the results of a large genome-wide association study. The newspaper quotes the researchers as saying: “This discovery demonstrates the power of genetics for defining diseases and establishing them as medical conditions.” It remains to be seen if any new preventive or curative treatments result from this study.

Where did the story come from?

Hreinn Stefansson and colleagues from research centres in Iceland, the US, Spain and the UK conducted this study. It was published in the peer-reviewed journal, the New England Journal of Medicine.

What kind of scientific study was this?

This genome-wide association study looked for particular gene sequences (variants) that are associated with restless leg syndrome that includes periodic limb movements in sleep. Researchers recruited 306 people with restless leg syndrome, who had periodic limb movements while they slept; at the same time, 15,664 people who did not have restless leg syndrome were recruited.The gene sequence for each person was analysed to test for variations that were more common in the people with restless leg syndrome.

To confrm these results, two further analyses were performed, in which and additional 311 cases and 1,895 controls from Iceland and the US were tested for this genetic association. The DNA sequence of 229 people who had restless leg syndrome but no periodic limb movements in sleep was also tested. The researchers also measured levels of serum ferritin in participants, as iron depletion has previously been associated with restless leg syndrome.

What were the results of the study?

In the main Icelandic sample of people with restless leg syndrome and periodic limb movements during sleep, the researchers found that there was an association with a gene variant within a gene called BTBD9 on chromosome 6. The same association was found in a second Icelandic sample and in the US sample. In people with restless leg syndrome who did not have periodic limb movements, there was no association with this gene variant. In people with restless leg syndrome and periodic limb movements in sleep, this gene variant was associated with about half of the cases. Also, in people who had this gene variant, serum ferritin levels were reduced by 13%.

What interpretations did the researchers draw from these results?

The researchers conclude that they have found a genetic variant within the BTBD9 gene, which is associated with an increased risk of restless leg syndrome and periodic limb movements in sleep. They state that the fact that the presence of this gene variant is associated with a reduction in iron stores 'is consistent with the suspected involvement of iron depletion in the pathogenesis of the disease'.

What does the NHS Knowledge Service make of this study?

This study was well conducted, and the results are reliable. The variant identified is associated with restless leg syndrome with periodic limb movement in sleep, but there may also be other genes that play a role in this condition. In particular, this gene variant was not associated with restless leg syndrome without periodic limb movements in sleep. While they found an association between the gene variant and lower levels of iron, it is not clear how the gene variant may influence iron levels or other processes that play a role in restless leg syndrome.

This study establishes an association between a gene mutation and a type of restless leg syndrome. The clinical implications of this are not clear

Dr Muir Gray adds...

This common condition is distressing to the individual affected and an effective treatment would bring relief to many. Even though this study gives us a better understanding of the condition, the translation of that into clinically useful treatments could take years.

NHS Attribution