Evidence map›Paper›PMID 37312046›Full record

ArticleBMC genomics2023

GBA1 in Parkinson's disease: variant detection and pathogenicity scoring matters.

Carolin Gabbert, Susen Schaake, Theresa Lüth, Christoph Much, Christine Klein, Jan O Aasly, Matthew J Farrer, Joanne Trinh

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Classification and Genotype-Phenotype Relationships of GBA1 Variants: MDSGene Systematic Review.Movement disorders : official journal of the Movement Disorder Society · 2025
    Pooled it
  2. E326KJournal of Parkinson's disease · 2026
    Article
  3. Article
  4. Clinical Utility ofGenes · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Consensus Guidance for Genetic Counseling in GBA1 Variants: A Focus on Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Carolin GabbertInstitute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany.
Susen SchaakeInstitute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany.
Theresa LüthInstitute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany.
Christoph MuchInstitute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany.
Christine KleinInstitute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany.
Jan O AaslyDepartment of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
Matthew J FarrerDepartment of Neurology, University of Florida, Gainesville, FL, USA.
Joanne TrinhInstitute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany. joanne.trinh@neuro.uni-luebeck.de.
University of Lübeck · DENorwegian University of Science and Technology · NOUniversity of Florida · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGBA1 variants are the strongest genetic risk factor for Parkinson's disease (PD). However, the pathogenicity of GBA1 variants concerning PD is still not fully understood. Additionally, the frequency of GBA1 variants varies widely across populations.

objectivesTo evaluate Oxford Nanopore sequencing as a strategy, to determine the frequency of GBA1 variants in Norwegian PD patients and controls, and to review the current literature on newly identified variants that add to pathogenicity determination.

methodsWe included 462 Norwegian PD patients and 367 healthy controls. We sequenced the full-length GBA1 gene on the Oxford Nanopore GridION as an 8.9 kb amplicon. Six analysis pipelines were compared using two aligners (NGMLR, Minimap2) and three variant callers (BCFtools, Clair3, Pepper-Margin-Deepvariant). Confirmation of GBA1 variants was performed by Sanger sequencing and the pathogenicity of variants was evaluated.

resultsWe found 95.8% (115/120) true-positive GBA1 variant calls, while 4.2% (5/120) variant calls were false-positive, with the NGMLR/Minimap2-BCFtools pipeline performing best. In total, 13 rare GBA1 variants were detected: two were predicted to be (likely) pathogenic and eleven were of uncertain significance. The odds of carrying one of the two common GBA1 variants, p.L483P or p.N409S, in PD patients were estimated to be 4.11 times the odds of carrying one of these variants in controls (OR = 4.11 [1.39, 12.12]).

conclusionsIn conclusion, we have demonstrated that Oxford long-read Nanopore sequencing, along with the NGMLR/Minimap2-BCFtools pipeline is an effective tool to investigate GBA1 variants. Further studies on the pathogenicity of GBA1 variants are needed to assess their effect on PD.

Indexed as

NanoporesParkinson DiseasePiper nigrumHigh-Throughput Nucleotide SequencingHumansVirulenceGBANanopore sequencingParkinson’s diseaseRisk factorVariants

Identifiers

PMID37312046
PMCPMC10262508
OpenAlexW4380483503

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.