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.
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.
Authors: Barbara Schormair; David Kemlink; Darina Roeske; Gertrud Eckstein; Lan Xiong; Peter Lichtner; Stephan Ripke; Claudia Trenkwalder; Alexander Zimprich; Karin Stiasny-Kolster; Wolfgang Oertel; Cornelius G Bachmann; Walter Paulus; Birgit Högl; Birgit Frauscher; Viola Gschliesser; Werner Poewe; Ines Peglau; Pavel Vodicka; Jana Vávrová; Karel Sonka; Sona Nevsimalova; Jacques Montplaisir; Gustavo Turecki; Guy Rouleau; Christian Gieger; Thomas Illig; H-Erich Wichmann; Florian Holsboer; Bertram Müller-Myhsok; Thomas Meitinger; Juliane Winkelmann Journal: Nat Genet Date: 2008-07-27 Impact factor: 38.330
Authors: Xianqin Zhang; Shenghan Chen; Shin Yoo; Susmita Chakrabarti; Teng Zhang; Tie Ke; Carlos Oberti; Sandro L Yong; Fang Fang; Lin Li; Roberto de la Fuente; Lejin Wang; Qiuyun Chen; Qing Kenneth Wang Journal: Cell Date: 2008-12-12 Impact factor: 41.582
Authors: Maria Teresa Bonati; Luigi Ferini-Strambi; Paolo Aridon; Alessandro Oldani; Marco Zucconi; Giorgio Casari Journal: Brain Date: 2003-06 Impact factor: 13.501
Authors: Jana Drgonova; Donna Walther; Katherine J Wang; G Luke Hartstein; Bryson Lochte; Juan Troncoso; Noriko Uetani; Yoichiro Iwakura; George R Uhl Journal: Mol Med Date: 2015-07-14 Impact factor: 6.354
Authors: Qinbo Yang; Lin Li; Qiuyun Chen; Nancy Foldvary-Schaefer; William G Ondo; Qing Kenneth Wang Journal: Sleep Med Date: 2011-09 Impact factor: 3.492
Authors: Lina Yin; Erica L Unger; Leslie C Jellen; Christopher J Earley; Richard P Allen; Ann Tomaszewicz; James C Fleet; Byron C Jones Journal: Am J Physiol Regul Integr Comp Physiol Date: 2012-03-28 Impact factor: 3.619
Authors: Myeong-Kyu Kim; Yong Won Cho; Won Chul Shin; Jae Wook Cho; Young Min Shon; Jee Hyun Kim; Kwang Ik Yang; Christopher J Earley; Richard P Allen Journal: Sleep Date: 2013-12-01 Impact factor: 5.849
Authors: Angela Roco; Félix Javier Jiménez-Jiménez; Hortensia Alonso-Navarro; Carmen Martínez; Martín Zurdo; Laura Turpín-Fenoll; Jorge Millán; Teresa Adeva-Bartolomé; Esther Cubo; Francisco Navacerrada; Ana Rojo-Sebastián; Lluisa Rubio; Marisol Calleja; José Francisco Plaza-Nieto; Belén Pilo-de-la-Fuente; Margarita Arroyo-Solera; Elena García-Martín; José A G Agúndez Journal: J Neural Transm (Vienna) Date: 2012-09-22 Impact factor: 3.575