SNPwatch: New Associations May Offer Insight into Restless Legs Syndrome

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

No one understands how or why millions of Americans are afflicted with restless legs syndrome, a “creepy-crawly” sensation that compels them to move their legs while lying in bed at night.

The phenomenon is so strange and poorly understood, in fact, that some physicians even question whether the seriousness and extent of restless legs syndrome has been over-hyped.

A report published today in Nature Genetics could change some minds about the mysterious condition. New research shows that two SNPs, both located in a gene that encodes a brain signaling protein, may influence who is affected by restless legs syndrome (RLS). A study of 2,458 sufferers and 4,749 people without the condition from Germany, Austria, The Czech Republic and Canada has shown that versions of both rs1975197 and rs4626664 increase the risk of having RLS. 23andMe customers can check their data for rs1975197 using our Browse Raw Data feature. According to the study, compared to the much more common GG genotype, each A at rs1975197 increases the odds of RLS by 1.31.

The riskier version of rs4626664 had a similar effect, with each copy increasing the odds of having RLS by 1.44 times. (23andMe does not report data for this SNP at this time) RLS has been recognized in the medical literature since 1683, but didn’t gain its official name until 1945. The involvement of genes in the disorder has been suspected since the 1920s. Studies of affected families have identified broad regions of the genome that could contain genes influencing RLS, and recently scientists have been narrowing in on various candidates using genome-wide association studies of SNPs.

In 2007 the same research group behind the new study by Schormair et al published results describing three other RLS-associated SNPs. One of these SNPs (rs3923809 in BTBD9) was replicated by a separate group and is described in detail in the 23andMe My Gene Journal (now called Health and Traits) article on Restless Legs Syndrome. The newly identified SNPs, rs1975197 and rs4626664, are located in PTPRD, a gene that encodes a signaling protein expressed in the brain. Mouse studies have shown that this protein is important for motor neuron development. These nerve cells connect the central nervous system to the musculature, making their involvement in RLS an attractive theory. RLS cannot be definitively diagnosed with a blood test or other measure.

Instead, patients are classified as having the disorder if the symptoms they describe fit with several criteria. Some have argued that “disease mongering” on the part of drug companies and the media has convinced healthy people that they have RLS and should seek treatment. As more genetic associations like those reported today are found for RLS, the underlying biology of the disorder may become more clear, allowing more definitive diagnoses.