CHICAGO — A group of German researchers have identified a fourth genetic risk variant for restless legs syndrome.
The PTPRD gene located on chromosome 9 joins a list of common risk variants found to be associated with the disorder. Carriers of one risk allele have a 50% increased risk of developing restless legs syndrome (RLS), Dr. Juliane Winkelmann said at the 12th International Congress of Parkinson's Disease and Movement Disorders.
Moreover, two of the four genes where the variants are located are clearly involved in early embryogenesis, suggesting that RLS may be a developmental disorder.
“It's possible that minor alterations of spinal neuron circuits in early embryonic stages—together with genetic and nongenetic risk factors such as aging or uremia—finally manifest the symptoms of restless legs syndrome,” she said.
RLS is a familial disorder in 40%-60% of patients and has a high concordance in twins. Previous linkage studies in families revealed several loci but failed to identify disorder-causing sequence variants.
In a previous genome-wide association study, Dr. Winkelmann of the Technical University of Munich and associates identified an association between RLS and variants in the MEIS1, BTBD9, and MAP2K5/LBXCOR1 genes (Nat. Genet. 2007;39:938-9).
The team expanded their sample size to 2,600 patients with RLS and 5,000 controls and focused on the the RLS3 region on chromosome 9.
Fine mapping identified the PTPRD gene, which is involved in axonal guidance during early embryonic development.
The association reached a genome-wide significance, with an odds ratio of more than 1.5, Dr. Winkelmann said at the international congress.
“The main thing we have to do now is to investigate if these genetic variants play a role in RLS in embryonic stages or if they have a completely different function in the adult nervous system,” she said.
During a discussion of the study, it was asked whether the variants are distributed less frequently is some populations, as epidemiologic studies have shown that RLS is present in about 10% of the population in Canada, the United States, and Europe but is less frequent in Asia.
The MEIS1 variant is less common in Asians, but this is not true of the other variants, Dr. Winkelmann responded.