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Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden

Ran, Caroline ; Brodin, Lovisa ; Forsgren, Lars ; Westerlund, Marie ; Ramezani, Mehrafarin ; Gellhaar, Sandra ; Xiang, Fengqing ; Fardell, Camilla ; Nissbrandt, Hans and Söderkvist, Peter , et al. (2016) In Neurobiology of Aging 45. p.5-212
Abstract

Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value =... (More)

Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gaucher's disease, GBA, Genetics, Lysosome, α-Synuclein
in
Neurobiology of Aging
volume
45
pages
5 - 212
publisher
Elsevier
external identifiers
  • scopus:84975110901
  • pmid:27255555
  • wos:000381092900024
ISSN
0197-4580
DOI
10.1016/j.neurobiolaging.2016.04.022
language
English
LU publication?
yes
id
5c1154bf-c829-4c2c-b321-4ad500d3e64b
date added to LUP
2016-07-12 12:49:05
date last changed
2025-01-12 08:48:34
@article{5c1154bf-c829-4c2c-b321-4ad500d3e64b,
  abstract     = {{<p>Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology.</p>}},
  author       = {{Ran, Caroline and Brodin, Lovisa and Forsgren, Lars and Westerlund, Marie and Ramezani, Mehrafarin and Gellhaar, Sandra and Xiang, Fengqing and Fardell, Camilla and Nissbrandt, Hans and Söderkvist, Peter and Puschmann, Andreas and Ygland, Emil and Olson, Lars and Willows, Thomas and Johansson, Anders and Sydow, Olof and Wirdefeldt, Karin and Galter, Dagmar and Svenningsson, Per and Belin, Andrea Carmine}},
  issn         = {{0197-4580}},
  keywords     = {{Gaucher's disease; GBA; Genetics; Lysosome; α-Synuclein}},
  language     = {{eng}},
  pages        = {{5--212}},
  publisher    = {{Elsevier}},
  series       = {{Neurobiology of Aging}},
  title        = {{Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden}},
  url          = {{http://dx.doi.org/10.1016/j.neurobiolaging.2016.04.022}},
  doi          = {{10.1016/j.neurobiolaging.2016.04.022}},
  volume       = {{45}},
  year         = {{2016}},
}