Family-based and population-based association studies validate PTPRD as a risk factor for restless legs syndrome

Qinbo Yang, Lin Li, Rong Yang, Gong Qing Shen, Qiuyun Chen, Nancy Foldvary-Schaefer, William G. Ondo, Qing Kenneth Wang

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Objective: We previously mapped a genetic locus for restless legs syndrome (RLS) to chromosome 9p22-24 (RLS3) and a later genome-wide association study (GWAS) implicated the PTPRD gene at the RLS3 locus as a susceptibility gene for RLS. However, from the standpoint of genetics, the GWAS association needs to be validated by independent studies. 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. Methods: We genotyped two intronic SNPs rs1975197 and rs4626664 in PTPRD in 144 family members from 15 families and a case control cohort of 189 patients and 560 controls. Direct DNA sequence analysis was used to screen coding exons and exon-intron boundaries of PTPRD for rare mutations. Results: A family-based sibling transmission disequilibrium test showed association of RLS with SNP rs1975197 (P = 0.015), but not with rs4626664 (P = 0.622). The association with rs1975197 was significantly replicated by a population-based case control association study (allelic P = 0.0004, odds ratio = 1.68; genotypic P = 0.0013 and 0.0003 for an additive and dominant model, respectively). One rare p.E1639D variant was identified in exon 39 in kindred RLS40005. The rare D1639 allele did not co-segregate with RLS in the family, suggesting that p.E1639D variant is not a causative mutation. Conclusions: This represents the first independent study to validate the association between PTPRD variants and RLS. Both family-based and population-based association studies suggest that PTPRD variant rs1975197 confers risk of RLS.

Original languageEnglish (US)
Pages (from-to)516-519
Number of pages4
JournalMovement Disorders
Issue number3
StatePublished - Feb 15 2011


  • Case-control association study
  • Family-based association study
  • PTPRD gene
  • Restless legs syndrome
  • Sibling transmission/disequilibrium test

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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