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

Research output: Contribution to journalArticle


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.


  • Caroline Ran
  • Lovisa Brodin
  • Lars Forsgren
  • Marie Westerlund
  • Mehrafarin Ramezani
  • Sandra Gellhaar
  • Fengqing Xiang
  • Camilla Fardell
  • Hans Nissbrandt
  • Peter Söderkvist
  • Andreas Puschmann
  • Emil Ygland
  • Lars Olson
  • Thomas Willows
  • Anders Johansson
  • Olof Sydow
  • Karin Wirdefeldt
  • Dagmar Galter
  • Per Svenningsson
  • Andrea Carmine Belin
External organisations
  • Karolinska Institutet
  • Karolinska University Hospital
  • Umeå University
  • University of Gothenburg
  • Linköping University
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences


  • Gaucher's disease, GBA, Genetics, Lysosome, α-Synuclein
Original languageEnglish
Pages (from-to)212.e5-212e.11
JournalNeurobiology of Aging
Publication statusPublished - 2016 Sep
Publication categoryResearch