Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson's Disease Cohorts

Jodi Maple-Grodem* (Corresponding Author), Kimberly C. Paul, Ingvild Dalen, Kathie J. Ngo, Darice Wong, Angus D. Macleod, Carl E. Counsell, David Backstrom, Lars Forsgren, Ole-Bjorn Tysnes, Cynthia D. J. Kusters, Brent L. Fogel, Jeff M. Bronstein, Beate Ritz, Guido Alves

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Background: Motor complications are a consequence of the chronic dopaminergic treatment of Parkinson's disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA-associated PD differ in their risk of developing motor complications compared to the general PD population.

Objective: To evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD.

Methods: Motor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models.

Results: In 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95% CI 0.47 to 1.26, p = 0.30) or MF (HR 1.19, 95% CI 0.84 to 1.70, p = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95% CI 0.55 to 2.14, p = 0.82) or MF (HR 1.22, 95% CI 0.74 to 2.04, p = 0.43).

Conclusion: This study does not provide evidence that GBA-carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA-associated PD.

Original languageEnglish
Pages (from-to)1569-1578
Number of pages10
Journal Journal of Parkinson's Disease
Issue number4
Publication statusPublished - 12 Oct 2021

Bibliographical note

The authors would like to thank all of the patients and controls for participation in each of the studies. Equally, we thank all members of each of the study
groups and other personnel for their contributions. Funding sources for the respective studies are as follows: The Norwegian ParkWest study has been
funded by the Research Council of Norway (177966), the Western Norway Regional Health Authority (911218), the Norwegian Parkinson’s Research
Foundation, and Rebergs Legacy. PINE study was supported by Parkinson’s UK (G0502, G0914, G1302), Scottish Government Chief Scientist Office,
BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, and RS MacDonald Trust. The NYPUM study has been funded by the Swedish Medical Research Council, the Swedish Parkinson’s disease Association, the Swedish Parkinson’s Foundation, Parkinson Research Foundation, Erling Persson Foundation, Kempe Foundation, the Swedish Brain Foundation (Hjarnfonden), and the Vasterbotten County Council. AAS, JMG and GA are supported by the Research Council of Norway (287842). BLF acknowledges support through
donations to the UCLA Clinical Neurogenomics Research Center. CK is supported by the NIH grant F32AG063442. The PEG study was supported by NIH/NIEHS grants R01-ES010544 and U54-ES012078. Publication of this manuscript was supported under the The Michael J. Fox Foundation: 2021 RFA: Accelerating Publication of Parkinson’s Disease Replication Data.

Data Availability Statement

The supplementary material is available in the electronic version of this article:


  • GBA
  • Parkinson's disease
  • motor complications
  • dyskinesias
  • motor fluctuations
  • RISK
  • GENE


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