Restless Legs Syndrome Foundation Blog

New Genes Discovered that Contribute to Risk of RLS

Last month, researchers reported the identification of thirteen new gene loci that increase the risk for developing restless legs syndrome. This is a major milestone in demonstrating the power of genomics and its capacity to locate genes responsible for certain diseases.

It has long been known that RLS runs in families. Parents with RLS often have children, or even grandchildren, that exhibit signs of restless legs. Many adults with RLS recall their parents experiencing RLS symptoms decades prior, before the disorder had a recognized name. However, discovering how and why this familial phenomenon occurs has been difficult.

To date, the most successful research method in searching for genes associated with RLS has been genome-wide association studies (GWAS). This strategy involves using a large pool of individuals -- divided into a group with RLS and a group without RLS -- and screening common variants in their DNA.

In 2007, a GWAS study in the Icelandic population, funded in part by the RLS Foundation grant to Dr. David Rye of Emory University, identified for the first time a gene variant on BTBD9 that was associated with the “risk” of developing RLS. Subsequent studies by Dr. Juliane Winkelmann of Technical University of Munich and others further broadened the number of genes that were potentially involved in the risk of developing RLS.

In this most recent study, "Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis," researchers from many countries in Europe and North America combined three GWAS datasets, totaling 15,126 individuals with RLS and 95,725 individuals without RLS. The researchers then went to work on searching for genome-wide signals. To confirm their results, they used data from an additional 30,770 individuals with RLS and 286,913 individuals without RLS to ensure that their data could be replicated. And it could.

The study revealed strong evidence for 19 genes that contribute to the risk of RLS, 13 of which were new discoveries. Additional analyses also found:

• The strongest risk factor for RLS was confirmed as gene locus MEIS1.
• A strong association was observed near the CRBN gene locus.

While last month's study did not prove that these 19 gene variants cause RLS, it is certain to help future research better understand the molecular causes of the disease, ultimately leading to the development of new treatment options for this serious neurological condition.

Genetic Connections Discovered Between Sleep and Some Medical Disorders

A recent study in December 2016 by a team of American and British researchers unearthed genetic connections between sleep disturbance and a range of medical disorders.

For the very first time, areas of the genome that are associated with sleep disturbance (like insomnia, excessive daytime sleepiness and restless legs syndrome) were identified, while also discovering new genetic links with several medical conditions, including RLS, schizophrenia and obesity.

How did they do it? Researchers studied the health and life history of more than 112,000 individuals taking part in the UK Biobank study. Participants reported their sleep duration, the degree of insomnia/daytime sleepiness, and then had their genes mapped. Health information including weight and disease diagnoses was also included. Researchers then compared the biological controllers of sleep duration, insomnia and excessive daytime sleepiness, and how these linked to the surveyed individuals.

These researchers discovered eight genes that may contribute to sleep issues - the first to be specifically linked to insomnia. Their findings revealed that a portion of the genes that are most strongly linked to sleep disturbances were also linked to RLS, insulin resistance, depression, schizophrenia and obesity.

This marks the first time that sleep disorders and these conditions have been connected at a molecular level, increasing our understanding of the relationship between biology and sleep.

The paper that resulted from the study, "Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits," was published in the scientific journal Nature Genetics. The article is available for purchase.

Read the HealthCanal article to learn more about this groundbreaking discovery!