Wen-Hua Sun, Claudia Schulte, Thomas Gasser, Manuela Tan, the Global Parkinson’s Genetic Program (GP2), Lasse Pihlstrøm, Pedro Chaná, Yeajin Song, Sara Bandrés‐Ciga, Cornelis Blauwendraat, Andrew Singleton, Mike A. Nalls, Hampton L. Leonard, Mie Rizig, Hirotaka Iwaki, Carlos Roberto de Mello Rieder, Ignácio F. Mata, Njideka Okubadejo, Emilia Gatto, Marcelo Kauffman, Claire E. Shepherd, Samson Khachatryan, Zaruhi Tavadyan, Julie Hunter, Kishore R. Kumar, Melina Ellis, Miguel E. Rentería, Sulev Kõks, Alexander Zimprich, Vítor Tumas, Sarah Camargos, Edward A. Fon, Ted Fon, Oury Monchi, Benjamin Pizarro Galleguillos, Patricio Olguı́n, Marcelo Miranda, M. Leonor Bustamante, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Gonzálo Arboleda, Jorge Orozco, Marlene Jiménez-Del-Río, Alvaro G. Hernandez, Mohamed Salama, Walaa A. Kamel, Yared Z. Zewde, Alexis Brice, Jean‐Christophe Corvol, Ana Westenberger, Christine Klein, Eva-Juliane Vollstedt, Harutyun Madoev, Joanne Trinh, Johanna Junker, Katja Lohmann, Anastasia Illarionova, Brit Mollenhauer, Franziska Hopfner, Günter U. Höglinger, Lara M. Lange, Manu Sharma, Sergiu Groppa, Zih‐Hua Fang, Albert Akpalu, Georgia Xiromerisiou, Georgios M. Hadjigeorgiou, Efthimios Dardiotis, Ioannis Dagklis, Ioannis Tarnanas, Leonidas Stefanis, María Stamelou, Alex Medina, Germaine Hiu-Fai Chan, Nelson Yuk-Fai Cheung, Nancy Y. Ip, Phillip Chan, Xiaopu Zhou, Asha Kishore, K. P. Divya, Pramod Kumar Pal, Prashanth Lingappa Kukkle, Roopa Rajan, Rupam Borgohain, Mehri Salari, Andrea Quattrone, Enza Maria Valente, Micol Avenali, Lucilla Parnetti, Tommaso Schirinzi, Manabu Funayama, Nobutaka Hattori, Tomotaka Shiraishi, Altynay Karimova, Gulnaz Kaishibayeva, Cholpon Shambetova, Rejko Krüger
Genome-wide association study of Parkinson's disease (PD) identified common variants associated with lysosomal mechanism, including TMEM175, SCARB2, and CTSB. We investigated the association between common and rare variants across populations using cohorts from the Global Parkinson's Genetics Program (GP2) (33,733 cases and 18,703 controls from ten ancestries). In the European cohort, we confirmed significant associations with PD risk for all known genetic risk variants across the three genes and TMEM175 p. Met393Thr as an independent genome-wide significant signal. Additionally, a novel independent signal, SCARB2 rs11547135, was detected. The burden analysis linked PD to SCARB2 in African American, Ashkenazi Jewish and East Asian cohorts. Single variants-based tests identified rare missense variants in SCARB2 in several populations. Our study reinforces the association of lysosomal genetic variants with PD risk, revealing genetic heterogeneity across populations.