Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
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 Swedis...
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Umeå universitet, Klinisk neurovetenskap
2016
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ftumeauniv:oai:DiVA.org:umu-126615 2023-10-09T21:54:32+02:00 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 Söderkvist, Peter Puschmann, Andreas Ygland, Emil Olson, Lars Willows, Thomas Johansson, Anders Sydow, Olof Wirdefeldt, Karin Galter, Dagmar Svenningsson, Per Belin, Andrea Carmine 2016 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-126615 https://doi.org/10.1016/j.neurobiolaging.2016.04.022 eng eng Umeå universitet, Klinisk neurovetenskap Neurobiology of Aging, 0197-4580, 2016, 45, s. 212.e5-212.e11 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-126615 doi:10.1016/j.neurobiolaging.2016.04.022 PMID 27255555 ISI:000381092900024 Scopus 2-s2.0-84975110901 info:eu-repo/semantics/openAccess Genetics Lysosome alpha-Synuclein Gaucher's disease GBA Neurosciences Neurovetenskaper Article in journal info:eu-repo/semantics/article text 2016 ftumeauniv https://doi.org/10.1016/j.neurobiolaging.2016.04.022 2023-09-22T13:58:45Z 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. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) Neurobiology of Aging 45 212.e5 212.e11 |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Genetics Lysosome alpha-Synuclein Gaucher's disease GBA Neurosciences Neurovetenskaper |
spellingShingle |
Genetics Lysosome alpha-Synuclein Gaucher's disease GBA Neurosciences Neurovetenskaper Ran, Caroline Brodin, Lovisa Forsgren, Lars Westerlund, Marie Ramezani, Mehrafarin Gellhaar, Sandra Xiang, Fengqing Fardell, Camilla Nissbrandt, Hans Söderkvist, Peter Puschmann, Andreas Ygland, Emil Olson, Lars Willows, Thomas Johansson, Anders Sydow, Olof Wirdefeldt, Karin Galter, Dagmar Svenningsson, Per Belin, Andrea Carmine Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden |
topic_facet |
Genetics Lysosome alpha-Synuclein Gaucher's disease GBA Neurosciences Neurovetenskaper |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Ran, Caroline Brodin, Lovisa Forsgren, Lars Westerlund, Marie Ramezani, Mehrafarin Gellhaar, Sandra Xiang, Fengqing Fardell, Camilla Nissbrandt, Hans Söderkvist, Peter Puschmann, Andreas Ygland, Emil Olson, Lars Willows, Thomas Johansson, Anders Sydow, Olof Wirdefeldt, Karin Galter, Dagmar Svenningsson, Per Belin, Andrea Carmine |
author_facet |
Ran, Caroline Brodin, Lovisa Forsgren, Lars Westerlund, Marie Ramezani, Mehrafarin Gellhaar, Sandra Xiang, Fengqing Fardell, Camilla Nissbrandt, Hans Söderkvist, Peter Puschmann, Andreas Ygland, Emil Olson, Lars Willows, Thomas Johansson, Anders Sydow, Olof Wirdefeldt, Karin Galter, Dagmar Svenningsson, Per Belin, Andrea Carmine |
author_sort |
Ran, Caroline |
title |
Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden |
title_short |
Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden |
title_full |
Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden |
title_fullStr |
Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden |
title_full_unstemmed |
Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden |
title_sort |
strong association between glucocerebrosidase mutations and parkinson's disease in sweden |
publisher |
Umeå universitet, Klinisk neurovetenskap |
publishDate |
2016 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-126615 https://doi.org/10.1016/j.neurobiolaging.2016.04.022 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Neurobiology of Aging, 0197-4580, 2016, 45, s. 212.e5-212.e11 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-126615 doi:10.1016/j.neurobiolaging.2016.04.022 PMID 27255555 ISI:000381092900024 Scopus 2-s2.0-84975110901 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1016/j.neurobiolaging.2016.04.022 |
container_title |
Neurobiology of Aging |
container_volume |
45 |
container_start_page |
212.e5 |
op_container_end_page |
212.e11 |
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1779318140683943936 |