Congratulations Dr. Matthew Farrer
Dr. Farrer’s paper of “Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism,” was published in the July issue of Movement Disorders.
Abstract:
Background: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with PD risk.
Objective: To investigate the impact of the MGS and lifestyle/environment on age at onset 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 AMP-PD, Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data was used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD risk factor questionnaire. 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 to controls (p=1.1 x 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 with 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.
Conclusion: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared to 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.