Genome-wide association and whole exome sequencing studies reveal a novel candidate locus for restless legs syndrome

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 COGS (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.