Ufuk Ergun1, Bahar Say1, Sezen Guntekin Ergun2, Ferda Emriye Percin3, Levent Inan4, Sukran Kaygisiz5, Pınar Gelener Asal6, Buket Yurteri7, Maksim Struchalin8, Dmitry Shtokalo9, Mehmet Ali Ergun10. 1. Kırıkkale University Faculty of Medicine, Department of Neurology, Kırıkkale, Turkey. 2. Hacettepe University Faculty of Medicine, Department of Medical Biology, Anakara, Turkey. 3. Gazi University Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey. 4. Ministry of Health Ankara Research and Training Hospital Neurology and Algology Department, Ankara, Turkey. 5. Ministry of Health Ordu University Traning and Research Hospital, Ordu, Turkey. 6. Dr. Suat Gunsel University of Kyrenia Hospital, Kyrenia, Turkish Republic of Northern Cyprus. 7. Hacettepe University Faculty of Medicine, Department of Pediatric Basic Sciences, Ankara, Turkey. 8. AcademGene Ltd, Russia. 9. AcademGene Ltd, Russia; A.P.Ershov Institute of Informatics Systems SB RAS, Russia. 10. Gazi University Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey. Electronic address: aliergun@gazi.edu.tr.
Abstract
INTRODUCTION: The restless legs syndrome (RLS) is a common heritable neurologic disorder which is characterized by an irresistible desire to move and unpleasant sensations in the legs. METHODS: We aim to identify new variants associated with RLS by performing genome-wide linkage and subsequent association analysis of forty member's family with history of RLS. RESULTS: We found evidence of linkage for three loci 7q21.11 (HLOD = 3.02), 7q21.13-7q21.3 (HLOD = 3.02) and 7q22.3 (HLOD = 3.09). Fine-mapping of those regions in association study using exome sequencing identified SEMA3A (p-value = 8.5·10-4), PPP1R9A (p-value = 7.2·10-4), PUS7 (p-value = 8.7·10-4), CDHR3 (p-value = 7.2·10-4), HBP1 (p-value = 1.5·10-4) and COG5 (p-value = 1.5·10-4) genes with p-values below significance threshold. CONCLUSION: Linkage analysis with subsequent association study of exome variants identified six new genes associated with RLS mapped on 7q21 and q22.
INTRODUCTION: The restless legs syndrome (RLS) is a common heritable neurologic disorder which is characterized by an irresistible desire to move and unpleasant sensations in the legs. METHODS: We aim to identify new variants associated with RLS by performing genome-wide linkage and subsequent association analysis of forty member's family with history of RLS. RESULTS: We found evidence of linkage for three loci 7q21.11 (HLOD = 3.02), 7q21.13-7q21.3 (HLOD = 3.02) and 7q22.3 (HLOD = 3.09). Fine-mapping of those regions in association study using exome sequencing identified SEMA3A (p-value = 8.5·10-4), PPP1R9A (p-value = 7.2·10-4), PUS7 (p-value = 8.7·10-4), CDHR3 (p-value = 7.2·10-4), HBP1 (p-value = 1.5·10-4) and COG5 (p-value = 1.5·10-4) genes with p-values below significance threshold. CONCLUSION: Linkage analysis with subsequent association study of exome variants identified six new genes associated with RLS mapped on 7q21 and q22.