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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism
Movement Disorders, Year 2023
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Description
Background: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk. Objective: To investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic PD (iPD). Methods: We included N = 486 patients with LRRK2-PD and N = 9259 with iPD from the Accelerating Medicines Partnership® Parkinson's Disease Knowledge Platform (AMP-PD), Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD-RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO. Results: Our derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10−8). We observed that higher MGS was significantly associated with earlier AAO in LRRK2-PD (P = 0.047, β = −1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, β = 0.22). There was a correlation between MGS and AAO in LRRK2-PD patients of European descent (P = 0.049, r = −0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = −0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, β = −5.65) in LRRK2-PD and with tobacco use (P = 0.010, β = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non-smokers. Conclusions: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene–environment interactions as modifiers of AAO in LRRK2-PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Authors & Co-Authors
Lüth, Theresa
Germany, Lubeck
Universität zu Lübeck
Gabbert, Carolin
Germany, Lubeck
Universität zu Lübeck
Koch, Sebastian
Germany, Kiel
Christian-albrechts-universität zu Kiel
König, I. R.
Germany, Lubeck
Universität zu Lübeck
Caliebe, Amke
Germany, Kiel
Christian-albrechts-universität zu Kiel
Laabs, Björn Hergen
Germany, Lubeck
Universität zu Lübeck
Hentati, F. F.
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Ben Sassi, Samia
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Amouri, Rim
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Spielmann, Malte
Germany, Lubeck
Universität zu Lübeck
Klein, Christine
Germany, Lubeck
Universität zu Lübeck
Grünewald, Anne
Germany, Lubeck
Universität zu Lübeck
Luxembourg, Esch-sur-alzette
University of Luxembourg
Farrer, Matthew J.
United States, Gainesville
University of Florida
Trinh, Joanne
Germany, Lubeck
Universität zu Lübeck
Statistics
Citations: 14
Authors: 14
Affiliations: 5
Identifiers
Doi:
10.1002/mds.29563
ISSN:
08853185
e-ISSN:
15318257
Research Areas
Genetics And Genomics
Substance Abuse
Study Design
Cross Sectional Study