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

Code ↔ Paper

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Paper

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The authors' code

TypeScript · 18 lines · 825 B · MIT

/**
* @file Align Utils
* @author Alexander Rose <[email hidden]>
* @private
*/
import Structure from '../structure/structure';
/**
* Perform structural superposition of two structures,
* optionally guided by a sequence alignment
* @param {Structure|StructureView} s1 - structure 1 which is superposed onto structure 2
* @param {Structure|StructureView} s2 - structure 2 onto which structure 1 is superposed
* @param {Boolean} [align] - guide the superposition by a sequence alignment
* @param {String} [sele1] - selection string for structure 1
* @param {String} [sele2] - selection string for structure 2
* @return {undefined}
*/
declare function superpose(s1: Structure, s2: Structure, align?: boolean, sele1?: string, sele2?: string): number | import("three").Matrix4 | undefined;
export { superpose };

align-utils.d.ts at commit 0db8803, under MIT · at the source

Overview

Authors: Lingyu Zhang¹, Qianqian Jin², Ruochen Du¹, Yuxiang Liang¹

ORCID iDs: Yuxiang Liang

Institutions: Shanxi Medical University (China)

Journal: International journal of molecular sciences, volume 27, issue 10, article 4446

Dates: received 12 March 2026; accepted 4 May 2026; published online 15 May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.3390/ijms27104446 · PMID 42196425 · PMCID PMC13206922 · OpenAlex W7161594834

Open access: gold, a free copy (OpenAlex)

Status: code verified

Categories: genetics / omics (modality), human (organism), sleep disorders (population), cellular / molecular (subfield)

Methods: Statistics

Keywords: restless legs syndrome, GLO1, proteome-wide association study, Mendelian randomization, drug target

MeSH: Brain*, Genome-Wide Association Study*, Lactoylglutathione Lyase*, Proteome*, Restless Legs Syndrome*, Genetic Predisposition to Disease, Humans, Molecular Docking Simulation, Polymorphism, Single Nucleotide, Proteomics, Quantitative Trait Loci (* major topic)

Topic: Restless Legs Syndrome Research (Epidemiology, Medicine), according to OpenAlex

Funding: Shanxi Science and Technology Department (202503021211130)

Citations: not cited yet (Europe PMC); 47 references in the paper

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 GLO1, along with GRWD1 and MAP2K5, as significantly associated with RLS. GLO1 was identified by brain-based SMR (p = 0.0001), colocalization (PP.H4 = 0.96), TWAS (p = 0.048), and was confirmed by plasma-based SMR (p = 3.16 × 10−9) as the only protein associated with RLS. PheWAS analysis, without associations for 783 non-RLS phenotypes, confirmed the specificity of GLO1. Among 27 predicted GLO1-targeting compounds, Gambierol had the strongest binding affinity (−8.3 kcal/mol). This proteogenomic study identifies GLO1 as a prioritized causal gene and promising drug target for RLS, combining brain and plasma data to provide new insights into pathogenesis and candidate drug development.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above.

arose/ngl

License: MIT

State: the link answers, verified on 28 September 2026

Evidence: files inventoried

Commit: 0db88033650614103be761f151efc923b66e977e, 3 September 2026

Languages: TypeScript (637), JavaScript (174), Python (3), Shell (3)

Size: 1,129 files, 817 scripts

Software Heritage: archived

Found in: the text, “4.10. Molecular Docking”

Holds: README, license file, tests, continuous integration, documentation

Not found: CITATION.cff, environment file

Availability: 1 check, the latest on 28 September 2026: the link answers

28 September 2026: the link answers

819 files

dist/declarations/align/align-utils.d.ts, TypeScript, 18 lines
dist/declarations/align/alignment.d.ts, TypeScript, 33 lines
dist/declarations/align/superposition.d.ts, TypeScript, 28 lines
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src/symmetry/unitcell.ts, TypeScript, 212 lines
src/trajectory/callback-trajectory.ts, TypeScript, 72 lines
src/trajectory/frames-trajectory.ts, TypeScript, 88 lines
src/trajectory/frames.ts, TypeScript, 18 lines
src/trajectory/remote-trajectory.ts, TypeScript, 101 lines
src/trajectory/structure-trajectory.ts, TypeScript, 69 lines
src/trajectory/trajectory-player.ts, TypeScript, 272 lines
src/trajectory/trajectory-utils.ts, TypeScript, 30 lines
src/trajectory/trajectory.ts, TypeScript, 625 lines
src/types.ts, TypeScript, 11 lines
src/ui/parameters.ts, TypeScript, 63 lines
src/utils.ts, TypeScript, 576 lines
src/utils/adjacency-list.ts, TypeScript, 64 lines
src/utils/binary-heap.ts, TypeScript, 154 lines
src/utils/bitarray.ts, TypeScript, 497 lines
src/utils/counter.ts, TypeScript, 121 lines
src/utils/edt.ts, TypeScript, 53 lines
src/utils/gzip-decompressor.ts, TypeScript, 27 lines
src/utils/io-buffer.ts, TypeScript, 517 lines
src/utils/kdtree.ts, TypeScript, 278 lines
src/utils/label-factory.ts, TypeScript, 118 lines
src/utils/netcdf-reader.ts, TypeScript, 616 lines
src/utils/parse-xml.ts, TypeScript, 123 lines
src/utils/picker.ts, TypeScript, 486 lines
src/utils/queue.ts, TypeScript, 50 lines
src/utils/radius-factory.ts, TypeScript, 103 lines
src/utils/registry.ts, TypeScript, 33 lines
src/version.ts, TypeScript, 15 lines
src/viewer/geometry-group.ts, TypeScript, 31 lines
src/viewer/gl-utils.ts, TypeScript, 200 lines
src/viewer/stats.ts, TypeScript, 63 lines
src/viewer/tiled-renderer.ts, TypeScript, 150 lines
src/viewer/viewer-constants.ts, TypeScript, 90 lines
src/viewer/viewer-utils.ts, TypeScript, 392 lines
src/viewer/viewer.ts, TypeScript, 1,409 lines
src/worker/worker-pool.ts, TypeScript, 66 lines
src/worker/worker-registry.ts, TypeScript, 31 lines
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src/writer/pdb-writer.ts, TypeScript, 171 lines
src/writer/sdf-writer.ts, TypeScript, 128 lines
src/writer/stl-writer.ts, TypeScript, 92 lines
src/writer/writer.ts, TypeScript, 46 lines
test/math/tests-array-utils.spec.ts, TypeScript, 195 lines
test/math/tests-matrix-utils.spec.ts, TypeScript, 72 lines
test/parser/kin-parser.test.ts, TypeScript, 75 lines
test/parser/tests-cif-parser.spec.ts, TypeScript, 81 lines
test/parser/tests-csv-parser.spec.ts, TypeScript, 22 lines
test/parser/tests-cube-parser.spec.ts, TypeScript, 23 lines
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test/parser/tests-dx-parser.spec.ts, TypeScript, 23 lines
test/parser/tests-dxbin-parser.spec.ts, TypeScript, 23 lines
test/parser/tests-gro-parser.spec.ts, TypeScript, 22 lines
test/parser/tests-json-parser.spec.ts, TypeScript, 21 lines
test/parser/tests-mmtf-parser.spec.ts, TypeScript, 71 lines
test/parser/tests-mol2-parser.spec.ts, TypeScript, 22 lines
test/parser/tests-mrc-parser.spec.ts, TypeScript, 37 lines
test/parser/tests-msgpack-parser.spec.ts, TypeScript, 23 lines
test/parser/tests-netcdf-parser.spec.ts, TypeScript, 30 lines
test/parser/tests-obj-parser.spec.ts, TypeScript, 23 lines
test/parser/tests-pdb-parser.spec.ts, TypeScript, 160 lines
test/parser/tests-pdbqt-parser.spec.ts, TypeScript, 26 lines
test/parser/tests-pqr-parser.spec.ts, TypeScript, 22 lines
test/parser/tests-sdf-parser.spec.ts, TypeScript, 61 lines
test/parser/tests-text-parser.spec.ts, TypeScript, 22 lines
test/parser/tests-xml-parser.spec.ts, TypeScript, 24 lines
test/selection/tests-selection.spec.ts, TypeScript, 920 lines
test/structure/tests-structure-utils.spec.ts, TypeScript, 51 lines
test/structure/tests-structure-view.spec.ts, TypeScript, 73 lines
test/structure/tests-structure.spec.ts, TypeScript, 67 lines
test/surface/tests-surface-utils.spec.ts, TypeScript, 40 lines
test/tests-utils.spec.ts, TypeScript, 51 lines
test/utils/tests-bitarray.spec.ts, TypeScript, 344 lines
test/utils/tests-kdtree.spec.ts, TypeScript, 47 lines
test/writer/stl-writer.spec.ts, TypeScript, 19 lines
test/writer/tests-pdb-writer.spec.ts, TypeScript, 103 lines
test/writer/tests-sdf-writer.spec.ts, TypeScript, 88 lines
LICENSE, License, 21 lines
README.md, Text, 88 lines

At the source: github.com/arose/ngl

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
817 scripts, each with its path and the digest of its content;
no match between paragraphs and code yet;
neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data Availability Statement

No new data were generated in this study. All data analyzed are publicly available summary statistics from the following sources: FinnGen RLS GWAS (https://www.finngen.fi/, accessed on 3 May 2026) and Verma et al. [20]; ROSMAP brain pQTL (https://adsp-fgc.niagads.org, accessed on 3 May 2026); Banner brain pQTL (described in Beach et al. [24] and Wingo et al. [22]); CommonMind Consortium (CMC) brain eQTL (http://CommonMind.org, accessed on 3 May 2026); eQTLGen blood eQTL (https://www.eqtlgen.org, accessed on 3 May 2026); UK Biobank Pharma Proteomics Project (UKB-PPP) plasma pQTL (https://registry.opendata.aws/, accessed on 3 May 2026). Supplementary Tables are included with the manuscript.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 5 keywords, 11 MeSH terms, 1 funder, 47 references.

Cite

This paper

Zhang, L., Jin, Q., Du, R., & Liang, Y. (2026). Integration of Brain Proteomes and Genome-Wide Association Data Identifies GLO1 as a Candidate Causal Gene and Therapeutic Target for Restless Legs Syndrome. International journal of molecular sciences, 27(10), 4446. https://doi.org/10.3390/ijms27104446

BibTeX

@article{zhang2026integration, author = {Zhang, Lingyu and Jin, Qianqian and Du, Ruochen and Liang, Yuxiang}, title = {{Integration of Brain Proteomes and Genome-Wide Association Data Identifies GLO1 as a Candidate Causal Gene and Therapeutic Target for Restless Legs Syndrome}}, journal = {International journal of molecular sciences}, year = {2026}, month = may, volume = {27}, number = {10}, pages = {4446}, publisher = {Multidisciplinary Digital Publishing Institute (MDPI)}, issn = {1422-0067}, doi = {10.3390/ijms27104446}, url = {https://doi.org/10.3390/ijms27104446}, pmid = {42196425}, pmcid = {PMC13206922} }

RIS

TY - JOUR AU - Zhang, Lingyu AU - Jin, Qianqian AU - Du, Ruochen AU - Liang, Yuxiang TI - Integration of Brain Proteomes and Genome-Wide Association Data Identifies GLO1 as a Candidate Causal Gene and Therapeutic Target for Restless Legs Syndrome T2 - International journal of molecular sciences J2 - Int J Mol Sci PY - 2026 DA - 2026/05/15 VL - 27 IS - 10 SP - 4446 SN - 1422-0067 PB - Multidisciplinary Digital Publishing Institute (MDPI) DO - 10.3390/ijms27104446 UR - https://doi.org/10.3390/ijms27104446 LA - en ER -

CSL-JSON

{ "id": "10.3390/ijms27104446", "type": "article-journal", "title": "Integration of Brain Proteomes and Genome-Wide Association Data Identifies GLO1 as a Candidate Causal Gene and Therapeutic Target for Restless Legs Syndrome", "container-title": "International journal of molecular sciences", "author": [ { "family": "Zhang", "given": "Lingyu" }, { "family": "Jin", "given": "Qianqian" }, { "family": "Du", "given": "Ruochen" }, { "family": "Liang", "given": "Yuxiang" } ], "container-title-short": "Int J Mol Sci", "volume": "27", "issue": "10", "page": "4446", "DOI": "10.3390/ijms27104446", "PMID": "42196425", "PMCID": "PMC13206922", "ISSN": "1422-0067", "publisher": "Multidisciplinary Digital Publishing Institute (MDPI)", "URL": "https://doi.org/10.3390/ijms27104446", "language": "en", "issued": { "date-parts": [ [ 2026, 5, 15 ] ] } }

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