Restless leg syndrome is a common condition among older adults, characterized by an unpleasant crawling sensation in the legs and an urge to move them. Despite its prevalence, little is known about its causes. Previous studies had identified 22 genetic risk loci associated with the condition, but no biomarkers for diagnosis had been identified. An international team of researchers led by the Helmholtz Munich Institute of Neurogenomics, TUM, and the University of Cambridge conducted a genome-wide association study to analyze data from over 100,000 patients and 1.5 million controls to uncover genetic clues to the syndrome.
The study, published in Nature Genetics, identified over 140 new genetic risk loci, increasing the total number known to 164, including genes related to nerve and brain function. Two genes involved in glutamate receptors 1 and 4, crucial for nerve and brain function, were identified as potential targets for existing drugs or new therapies. The researchers also found no strong genetic differences between men and women, despite the syndrome being more common in women. This suggests a complex interaction of genetics and environmental factors, including hormones, may explain gender differences observed in the condition.
The researchers used Mendelian randomization, a technique that uses genetic information to examine cause-and-effect relationships, to understand how restless leg syndrome might affect overall health. They found that the syndrome increases the risk of developing diabetes. Despite previous theories linking low iron levels in the blood to the syndrome, the researchers did not find strong genetic links to iron metabolism. However, they acknowledge that iron deficiency and reduced dopamine levels may still play a role in the development of the condition.
By understanding the genetic basis of restless leg syndrome, the researchers hope to find better ways to manage and treat the condition, potentially improving the lives of millions of affected individuals worldwide. Co-author Dr. Steven Bell from the University of Cambridge stated that this study is the largest of its kind into the condition, emphasizing the significance of the findings in advancing our understanding of restless leg syndrome. The ability to predict the risk of the syndrome and potentially prevent its onset marks a significant advancement in the field, providing hope for more effective treatments in the future.
The researchers suggest that by using basic information like age, sex, and genetic markers, it is possible to accurately predict who is more likely to have severe restless leg syndrome in nine out of ten cases. This personalized approach to risk assessment could help identify individuals at greatest risk of the condition and guide targeted treatment strategies. Early trials of drugs targeting glutamate receptors have shown promising results in patients with restless leg syndrome, highlighting the potential for new therapeutic options based on the genetic findings.
Overall, the study sheds light on the genetic underpinnings of restless leg syndrome, revealing new potential targets for treatment and providing insight into the complex interplay of genetics and environmental factors in the development of the condition. The ability to predict and potentially prevent the onset of restless leg syndrome represents a significant milestone in the field, offering hope for more effective management and improved quality of life for individuals affected by the condition.
