Integration of Brain Proteomes and Genome-Wide Association Data Identifies GLO1 as a Candidate Causal Gene and Therapeutic Target for Restless Legs Syndrome.

Lingyu Zhang, Qianqian Jin, Ruochen Du, Yuxiang Liang

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Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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4 authors.

Lingyu ZhangShanxi Key Laboratory of Human Disease and Animal Models, Experimental Animal Center of Shanxi Medical University, Taiyuan 030001, China.

Qianqian JinDepartment of Forensic Pathology, Shanxi Medical University, Taiyuan 030001, China.

Ruochen DuShanxi Key Laboratory of Human Disease and Animal Models, Experimental Animal Center of Shanxi Medical University, Taiyuan 030001, China.

Yuxiang LiangShanxi Key Laboratory of Human Disease and Animal Models, Experimental Animal Center of Shanxi Medical University, Taiyuan 030001, China.ORCID 0000-0003-0590-1724

Funding

Shanxi Science and Technology Department 202503021211130

6 · The paper itself

Abstract

Restless legs syndrome (RLS) is a common sensorimotor disorder with limited treatment options and incompletely understood pathophysiology. Genome-wide association studies have identified numerous risk loci, but translating these findings into causal genes and therapeutic targets remains challenging. We performed a proteome-wide association study (PWAS) integrating RLS genome-wide association study (GWAS) data from FinnGen with two brain pQTL datasets (ROSMAP and Banner). We validated the identified proteins using TWAS, SMR, and colocalization analyses using brain pQTL and eQTL datasets. To further investigate peripheral protein associations, we performed SMR using plasma pQTL data from the UK Biobank Pharma Proteomics Project (UKB-PPP). We also conducted a phenome-wide association study (PheWAS) to screen for potential off-target effects of the prioritized genes, followed by drug prediction using DSigDB and molecular docking. PWAS identified

Indexed as

BrainGenome-Wide Association StudyLactoylglutathione LyaseProteomeRestless Legs SyndromeGenetic Predisposition to DiseaseHumansMolecular Docking SimulationPolymorphism, Single NucleotideProteomicsQuantitative Trait LociLactoylglutathione LyaseProteomedrug targetGLO1Mendelian randomizationproteome-wide association studyrestless legs syndrome

Identifiers

PMID42196425

DOI10.3390/ijms27104446

PMCPMC13206922

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.