PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome

Juliane Winkelmann and colleagues report that two common variants in the 5′ UTR of PTPRD are independently associated with restless legs syndrome. PTPRD encodes a receptor-like protein tyrosine phosphatase previously implicated in axon guidance and motor neuron development. We identified association of restless legs syndrome (RLS) with PTPRD at 9p23–24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5′ UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P nominal/λ corrected = 5.91 × 10 −10 , odds ratio (OR) = 1.44; rs1975197, P nominal/λ corrected = 5.81 × 10 −9 , OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS.