A Genetic Step For Restless Leg Syndrome

Juliane Winkelmann and colleagues report a genome-wide association study (GWAS) of 401 individuals with a family history of RLS and 1,644 controls in Germany, with findings replicated in two independent cohorts in Germany and Canada. Statistically significant evidence was found for novel association of three genetic regions with RLS. While previous studies have suggested an important role for iron deficiency in RLS, the three regions here were not directly involved in iron metabolism, although indirect mechanisms may be suggested. Together, these genetic loci are able to explain a large proportion of the risk, with an estimated population attributable risk of 68%-74% in the populations examined here.

In a complementary study to be published at the same time in the New England Journal of Medicine (DOI: 10.1056/NEJMoa072743), Kari Stefansson and colleagues report a GWAS study on RLS and Periodic Limb Movements (PLM) - a related disorder characterized by limb or leg twitches - which finds one significantly associated genetic region.

While there has been some previous evidence for heritability of RLS, these papers represent the first identification of specific genetic regions significantly associated with RLS susceptibility. The gene candidates identified may prove useful in continuing studies to understand the mechanism underlying this disorder, as well as in developing drug targets.

Author contacts:

Juliane Winkelmann (Max Planck Institute of Psychiatry, Munich, Germany)
E-mail: janew@mpipsykl.mpg.de

Abstract available online.

(C) Nature Genetics press release.

Message posted by: Trevor M. D'Souza