Work

Ancestry-specific and multi-ancestry genome-wide association studies of restless legs syndrome

Year: 2026

Type: article

Study design: Observational Study

Abstract: Restless legs syndrome is a neurological disorder that disrupts sleep and quality of life, but its genetics have mostly been studied in individuals of European ancestry. Here, we perform GWAS of restless legs syndrome using data from individuals of African, Latin American, and European ancestry, followed by a multi-ancestry meta-analysis. We leverage biobank-based cohorts that established RLS diagnosis using validated clinical criteria, allowing for precise phenotypic characterization. We perform ancestry-specific association studies and post-GWAS analyses to prioritize candidate genes. Our analyses reveal ancestry differences in the genetics of restless legs syndrome. At the MEIS1 and BTBD9 loci, lead variants showed lower allele frequencies and did not reach genome-wide significance in African ancestry. We identify ancestry-specific and shared risk loci, including novel associations near GYPC/TEX51 and PRIMA1 in African ancestry and ISX in Latin American ancestry. The European meta-analysis identifies 11 additional loci and replicates 50 previously reported associations. The combined multi-ancestry analysis finds ten new loci. This multi-ancestry study broadens the genetic understanding of restless legs syndrome, and the absence or reduced frequency of key European restless legs syndrome alleles in individuals of African ancestry provides insights into known epidemiological differences.

Source: Nature Communications

DOI: 10.1038/s41467-026-78592-9

Authors: Fulya Akçimen, Miranda Medeiros, Katie L. J. Cederberg, Marzieh Khani, Andrew B. Roth, Mike A. Nalls, Sara Bandres-Ciga, Patrick A. Dion, Guy Rouleau, Emmanuel Mignot

Institutions: National Institutes of Health, National Institute on Aging, Montreal Neurological Institute and Hospital, McGill University, Stanford Medicine, Stanford University, National Institute of Neurological Disorders and Stroke

Language: English

Topic: Restless Legs Syndrome Research

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: U.S. Department of Health and Human Services, Government of Canada, National Institutes of Health, Canadian Institutes of Health Research

Awards: Illinois Precision Medicine Consortium , Healthy Americas: All of Us Research Program, G2392925134, Empowerment-focused Outreach, Education and Enrollment of Tennessee Older Adults in the All of Us Research Program through Community Efforts by FiftyForward, Research Matters: Creating Possibilities to Achieve Health and Wellness for All of Us Research Program, Precision Medicine Initiative Cohort Program Biobank, Communications Design and Development for NIH Precision Medicine Initiative Research Projects, New York City Consortium for Precision Medicine, Technology to Empower Changes in Health (TECH) Network Participant Technologies Center, University of Arizona-Banner Health All of Us Research Program , The New England Precision Medicine Consortium of the All of Us Research Program, G5725958272, All of Us Wisconsin , Data and Research Support Center , All of Us Pennsylvania, Trans-America Consortium of the Health Care Systems Research Network for the All of Us Research Program, Southern All of Us Network, G7024292332, G724077961, SouthEast Enrollment Center (SEEC) , Adaptive Platform for Personalized Engagement, California Precision Medicine Research Program Consortium, Communication Implementation and Coordination for NIH Precision Medicine Initiative Research Projects, PRIDEnet for the All of Us Research Program

OpenAlex ID: W7160316914

FWCI:

Cites: 54

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Related to: 10