Age at Onset of Parkinson’s Disease Among Ashkenazi Jewish Patients: Contribution of Environmental Factors, LRRK2 p.G2019S and GBA p.N370S Mutations

Article type: Research Article

Authors: Yahalom, Gilad^{a; b; c; d; *} | Rigbi, Amihai^e | Israeli-Korn, Simon^{b; c; d; f} | Krohn, Lynne^{g; h} | Rudakou, Uladzislau^{g; h} | Ruskey, Jennifer A.^{g; i} | Benshimol, Lior^b | Tsafnat, Tal^b | Gan-Or, Ziv^{g; h; i} | Hassin-Baer, Sharon^{b; c; d; f} | Greenbaum, Lior^{d; f; j}

Affiliations: [a] Movement Disorders Clinic and Department of Neurology, Shaare Zedek Medical Center, Jerusalem | [b] Movement Disorders Institute, Sheba Medical Center, Tel Hashomer, Israel | [c] Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel | [d] Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel | [e] Faculty of Education, Beit Berl College, Kfar Saba, Israel | [f] Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel | [g] Montreal Neurological Institute, McGill University, Montréal, QC, Canada | [h] Department of Human Genetics, McGill University, Montréal, QC, Canada | [i] Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada | [j] The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel

Correspondence: [*] Correspondence to: Gilad Yahalom, Movement Disorders Clinic, Department of Neurology, Shaare Zedek Medical Center, Jerusalem, Israel. Tel.: +972 2 6555912; Fax: +972 2 6666444; E-mail: [email protected].

Abstract: Background:Both genetic and environmental factors contribute to Parkinson’s disease (PD) risk. Objective:We investigated the potential association of several relevant variables with PD age at onset (AAO), focusing on LRRK2 p.G2019S and GBA p.N370S mutations. Methods:Ashkenazi Jewish (AJ) PD patients, screened for LRRK2 and GBA mutations, underwent an interview regarding exposure to the following environmental and lifestyle factors: cigarette smoking, consumption of coffee, tea and alcohol, history of head injury and rural living. Multivariate linear regression (adjusted for sex) was used to examine the association with AAO, and models included LRRK2 and GBA mutation status (carrier/non-carriers), single environmental variable and their interactions terms, as independent variables. Results:225 Israeli AJ PD patients were enrolled: 65 LRRK2 p.G2019S mutation carriers, 60 GBA p.N370S carriers and 100 non-carries of both mutations. In the dichotomized exposure/non-exposure analyses, positive LRRK2 p.G2019S status was associated with younger AAO in all models, at nominal or near significant levels (p = 0.033–0.082). Cigarette smoking was associated with older AAO (p = 0.032), and the interaction between GBA p.N370S and history of head injury was associated with younger AAO (p = 0.049), both at nominal significance. There was no indication of a consistent main effect for GBA p.N370S status or significant LRRK2 p.G2019S-environmental factor interaction. In the dose-dependent analysis, increased coffee and tea consumption levels were associated with older AAO (p = 0.001 and p = 0.002, respectively). Conclusions:Our results suggest that both genetic and environmental factors may affect AAO in PD patients, but validation in additional samples is required.

Keywords: Parkinson’s disease, age at onset, GBA p.N370S, LRRK2 p.G2019S, environmental factors, lifestyle habits, smoking, caffeine, tea, head injury, gene-environment interaction

DOI: 10.3233/JPD-191829

Journal: Journal of Parkinson's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2020