Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients

Aleksandra A. Szwedo, Camilla Christina Pedersen, Anastasia Ushakova, Lars Forsgren, Ole-Bjørn Tysnes, Carl E. Counsell, Guido Alves, Johannes Lange, Angus D. Macleod, Jodi Maple-Grødem* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Objectives: To evaluate the impact of SNCA polymorphisms originally identified as risk factors for Parkinson's disease (PD) on the clinical presentation and progression of the disease in a large cohort of population-based patients with incident PD.Methods: Four hundred thirty-three patients and 417 controls from three longitudinal cohorts were included in the study. Disease progression was recorded annually for up to 9 years using the Unified Parkinson's Disease Rating Scale (UPDRS) or Mini-Mental State Examination. Genotypes for five variants within the SNCA locus (rs2870004, rs356182, rs5019538, rs356219, and rs763443) were determined. We studied the association between each variant and disease progression using linear mixed-effects regression models.Results: The clinical profile of the patients with PD at the point of diagnosis was highly uniform between genotype groups. The rs356219-GG genotype was associated with a higher UPDRS II score than A-allele carriers (β = 1.52; 95% confidence interval 0.10–2.95; p = 0.036), but no differences were observed in the rate of progression of the UPDRS II scores. rs356219-GG was also associated with a faster annual change in Mini-Mental State Examination score compared with A-carriers (β = 0.03; 95% confidence interval 0.00–0.06; p = 0.043).Conclusions: We show that the known PD-risk variant rs356219 has a minor effect on modifying disease progression, whereas no differences were associated with rs2870004, rs356182, rs5019538, and rs763443. These findings suggest that SNCA variants associated with PD risk may not be major driving factors to the clinical heterogeneity observed for PD.
Original languageEnglish
Article number620585
Number of pages7
JournalFrontiers in Neurology
Publication statusPublished - 10 Feb 2021

Bibliographical note

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), and the Norwegian Parkinson’s Disease Association. PINE study was supported by Parkinson’s UK (G0502, G0914, and G1302), Scottish
Government Chief Scientist Office, BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, and RS
MacDonald Trust. The Swedish Medical Research Council, the Swedish Parkinson’s Disease Association, the Swedish
Parkinson’s Foundation, Erling Persson Foundation, Kempe Foundation, and the Västerbotten County Council have funded
the NYPUM study. The Research Council of Norway (287842) supported AS, JM-G, and GA.
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.


  • SNCA
  • Parkinson disease
  • disease progression
  • Genetic association
  • cognitive impairment
  • Parkinson's disease
  • genetic association
  • Parkinson&apos
  • s disease


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