Recent genome-wide association studies have identified variants within intronic or intergenic regions of MEIS1, BTBD9, and MAP2K5/LBXCOR1, and PTPRD, raising new pathological hypotheses for RLS.
Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD.
In this study, we used both family-based and population-based association studies to assess the association between PTPRD and RLS in an American Caucasian population.
These studies have identified four gene variants associated with restless legs syndrome (BTBD9, MEIS1, MAP2K5/LBXCOR1, and PTPRD) and two variants associated with narcolepsy (one in the T-cell receptor α locus and another between CPT1B and CHKB).
A modest association between the PTPRD variant rs4626664 and uremic RLS (odds ratio 1.52, 95% CI 1.03-2.23, P = 0.03) and a trend that TOX3/BC034767 variant rs3104767 may associate with the occurrence of RLS were observed in our dialysis population (odds ratio 1.74, 95% CI 0.97-3.11, P = 0.06).
Although to date the causative gene(s) has(ve) not been definitively identified, a number of variants of several genes, most of them through GWAS, have been associated with RLS risk, the strongest candidates being variants of PTPRD, BTBD9, and MEIS1 genes.