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

Ergun, UfukSay, BaharErgun, Sezen GuntekinPercin, Ferda EmriyeInan, LeventKaygisiz, SukranAsal, Pinar Gelener2025-01-212025-01-2120211769-72121878-0849https://doi.org/10.1016/j.ejmg.2021.104186https://hdl.handle.net/20.500.12587/24870Introduction: 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.eninfo:eu-repo/semantics/closedAccessRestless legs syndrome; Microarray; Linkage analysis; Genome wide association; Whole exome sequencingGenome-wide association and whole exome sequencing studies reveal a novel candidate locus for restless legs syndromeArticle64410.1016/j.ejmg.2021.1041862-s2.0-8510211712533662638Q3WOS:000635182200003Q3