Relevant conflicts of interest/financial disclosures: Dr. N. Foldvary receives research support from Glaxo Smith Kline, Inc., and Dr. W.G. Ondo is a speaker and consultant for Glaxo Smith Kline, Inc., Allergan, Ipsen, TEVA, Lundbeck, and Novartis. Other authors report no disclosures. Full financial disclosures and author roles may be found in the online version of this article.
Family-based and population-based association studies validate PTPRD as a risk factor for restless legs syndrome †
Article first published online: 24 JAN 2011
Copyright © 2011 Movement Disorder Society
Volume 26, Issue 3, pages 516–519, 15 February 2011
How to Cite
Yang, Q., Li, L., Yang, R., Shen, G.-Q., Chen, Q., Foldvary-Schaefer, N., Ondo, W. G. and Wang, Q. K. (2011), Family-based and population-based association studies validate PTPRD as a risk factor for restless legs syndrome . Mov. Disord., 26: 516–519. doi: 10.1002/mds.23459
- Issue published online: 31 MAR 2011
- Article first published online: 24 JAN 2011
- Manuscript Accepted: 7 SEP 2010
- Manuscript Revised: 12 AUG 2010
- Manuscript Received: 15 APR 2010
- NIH. Grant Number: P50 HL077107
- China Scholarship Council
- Hubei Natural Science Funds. Grant Number: 2008CDA047
- PTPRD gene;
- sibling transmission/disequilibrium test;
- restless legs syndrome;
- family-based association study;
- case-control association study
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.
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.
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.
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. © 2011 Movement Disorder Society