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TMEM175, SCARB2 and CTSB associations with Parkinson's disease risk across populations.
Sun, W. (First author)DZNE* ; Schulte, C.DZNE* ; Gasser, T.DZNE* ; Tan, M. ; Program, G. P. G. (Collaboration Author) ; Pihlstrøm, L. (Contributor) ; Chana, P. (Contributor) ; Song, Y. (Contributor) ; Bandres-Ciga, S. (Contributor) ; Blauwendraat, C. (Contributor) ; Singleton, A. (Contributor) ; Nalls, M. A. (Contributor) ; Leonard, H. (Contributor) ; Rizig, M. (Contributor) ; Iwaki, H. (Contributor) ; Rieder, C. (Contributor) ; Mata, I. F. (Contributor) ; Okubadejo, N. (Contributor) ; Gatto, E. M. (Contributor) ; Kauffman, M. (Contributor) ; Shepherd, C. E. (Contributor) ; Khachatryan, S. (Contributor) ; Tavadyan, Z. (Contributor) ; Hunter, J. (Contributor) ; Kumar, K. (Contributor) ; Ellis, M. (Contributor) ; Rentería, M. E. (Contributor) ; Koks, S. (Contributor) ; Zimprich, A. (Contributor) ; Tumas, V. (Contributor) ; Camargos, S. (Contributor) ; Fon, E. A. (Contributor) ; Fon, T. (Contributor) ; Monchi, O. (Contributor) ; Galleguillos, B. P. (Contributor) ; Olguin, P. (Contributor) ; Miranda, M. (Contributor) ; Bustamante, M. L. (Contributor) ; Tang, B. (Contributor) ; Shang, H. (Contributor) ; Guo, J. (Contributor) ; Chan, P. (Contributor) ; Luo, W. (Contributor) ; Arboleda, G. (Contributor) ; Orozco, J. (Contributor) ; Del Rio, M. J. (Contributor) ; Hernandez, A. (Contributor) ; Salama, M. (Contributor) ; Kamel, W. A. (Contributor) ; Zewde, Y. Z. (Contributor) ; Brice, A. (Contributor) ; Corvol, J.-C. (Contributor) ; Westenberger, A. (Contributor) ; Klein, C. (Contributor) ; Vollstedt, E.-J. (Contributor) ; Madoev, H. (Contributor) ; Trinh, J. (Contributor) ; Junker, J. (Contributor) ; Lohmann, K. (Contributor) ; Illarionova, A. (Contributor)Extern* ; Mollenhauer, B. (Contributor)Extern* ; Hopfner, F. (Contributor)Extern* ; Höglinger, G. (Contributor)Extern* ; Lange, L. M. (Contributor) ; Sharma, M. (Contributor) ; Groppa, S. (Contributor) ; Fang, Z.-H. (Contributor)Extern* ; Akpalu, A. (Contributor) ; Xiromerisiou, G. (Contributor) ; Hadjigeorgiou, G. (Contributor) ; Dardiotis, E. (Contributor) ; Dagklis, I. (Contributor) ; Tarnanas, I. (Contributor) ; Stefanis, L. (Contributor) ; Stamelou, M. (Contributor) ; Medina, A. (Contributor) ; Chan, G. H. (Contributor) ; Cheung, N. Y. (Contributor) ; Ip, N. (Contributor) ; Chan, P. (Contributor) ; Zhou, X. (Contributor) ; Kishore, A. (Contributor) ; Divya, K. P. (Contributor) ; Pal, P. (Contributor) ; Kukkle, P. L. (Contributor) ; Rajan, R. (Contributor) ; Borgohain, R. (Contributor) ; Salari, M. (Contributor) ; Quattrone, A. (Contributor)Extern* ; Valente, E. M. (Contributor) ; Avenali, M. (Contributor) ; Parnetti, L. (Contributor) ; Schirinzi, T. (Contributor) ; Funayama, M. (Contributor) ; Hattori, N. (Contributor) ; Shiraishi, T. (Contributor) ; Karimova, A. (Contributor) ; Kaishibayeva, G. (Contributor) ; Shambetova, C. (Contributor) ; Krüger, R. (Contributor) ; Tan, A. H. (Contributor) ; Ahmad-Annuar, A. (Contributor) ; Lim, S.-Y. (Contributor) ; Tay, Y. W. (Contributor) ; Norlinah, M. I. (Contributor) ; Azmin, S. (Contributor) ; Murad, N. A. A. (Contributor) ; Martinez-Ramirez, D. (Contributor) ; Rodriguez-Violante, M. (Contributor) ; Reyes-Pérez, P. (Contributor) ; Tserensodnom, B. (Contributor) ; Ojha, R. (Contributor) ; Anderson, T. J. (Contributor) ; Pitcher, T. L. (Contributor) ; Ojo, O. (Contributor) ; Aasly, J. O. (Contributor) ; Ur-Rehman, S. (Contributor) ; Cornejo-Olivas, M. (Contributor) ; Doquenia, M. L. (Contributor) ; Rosales, R. (Contributor) ; Vinuela, A. (Contributor) ; Iakovenko, E. (Contributor) ; Mubarak, B. A. (Contributor) ; Umair, M. (Contributor) ; Tan, E.-K. (Contributor) ; Amod, F. (Contributor) ; Carr, J. (Contributor) ; Bardien, S. (Contributor) ; Jeon, B. (Contributor) ; Kim, Y. J. (Contributor) ; Cubo, E. (Contributor) ; Alvarez, I. (Contributor) ; Hoenicka, J. (Contributor) ; Beyer, K. (Contributor) ; Pastor, P. (Contributor) ; El-Sadig, S. (Contributor) ; Zweier, C. (Contributor) ; Krack, P. (Contributor) ; Lin, C.-H. (Contributor) ; Wu, R.-M. (Contributor) ; Wu, H.-C. (Contributor) ; Wu, Y.-R. (Contributor) ; Kung, P.-J. (Contributor) ; Wu, S. (Contributor) ; Amouri, R. (Contributor) ; Ben Sassi, S. (Contributor) ; Başak, A. N. (Contributor) ; Çakmak, Ö. Ö. (Contributor) ; Ertan, S. (Contributor) ; Genc, G. (Contributor) ; Martínez-Carrasco, A. (Contributor) ; Schrag, A. (Contributor) ; Schapira, A. (Contributor) ; Stafford, E. J. (Contributor) ; Houlden, H. (Contributor) ; Morris, H. R. (Contributor) ; Hardy, J. (Contributor) ; Wood, N. (Contributor) ; Okunoye, O. (Contributor) ; Kaiyrzhanov, R. (Contributor) ; Weil, R. (Contributor) ; Jasaitye, S. (Contributor) ; Obese, V. (Contributor) ; Carroll, C. (Contributor) ; Bale, C. (Contributor) ; Grosset, D. (Contributor) ; Mok, K. Y. (Contributor) ; Williams, N. (Contributor) ; Lewis, P. A. (Contributor) ; Love, S. (Contributor) ; Stott, S. (Contributor) ; Espay, A. (Contributor) ; Marsili, L. (Contributor) ; O'Grady, A. (Contributor) ; Siddiqi, B. (Contributor) ; Casey, B. (Contributor) ; Fiske, B. (Contributor) ; Comart, C. (Contributor) ; Solle, J. C. (Contributor) ; Murphy, K. (Contributor) ; Kuhl, M. (Contributor) ; Louie, N. (Contributor) ; Chowdhury, S. (Contributor) ; Sherer, T. (Contributor) ; Sobering, A. K. (Contributor) ; Jonas, C. (Contributor) ; Cruchaga, C. (Contributor) ; Pantazis, C. B. (Contributor) ; Wegel, C. (Contributor) ; Hall, D. (Contributor) ; Shamim, E. (Contributor) ; Williamson, J. (Contributor) ; Riley, E. (Contributor) ; Dumanis, S. (Contributor) ; Serrano, G. E. (Contributor) ; Beach, T. (Contributor) ; Chen, H. (Contributor) ; Sarmiento, I. J. K. (Contributor) ; Mencacci, N. E. (Contributor) ; Lubbe, S. (Contributor) ; Jankovic, J. (Contributor) ; Inca-Martinez, M. (Contributor) ; Shulman, J. (Contributor) ; Nuytemans, K. (Contributor) ; Kieburtz, K. (Contributor) ; Markopoulou, K. (Contributor) ; Marek, K. (Contributor) ; Chahine, L. M. (Contributor) ; Ruffrage, L. (Contributor) ; Dean, M. (Contributor) ; Shulman, L. (Contributor) ; Albin, R. (Contributor) ; Alcalay, R. (Contributor) ; Walker, R. (Contributor) ; Xie, T. (Contributor) ; Foroud, T. (Contributor) ; Nguyen, D. (Contributor) ; Nguyen, T. (Contributor) ; Atadzhanov, M. (Contributor)
2025
Springer Nature
[London]
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Please use a persistent id in citations: doi:10.1038/s41531-025-01180-z
Abstract: 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.
Contributing Institute(s):
- Parkinson Genetics (AG Gasser)
Research Program(s):
- 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
Appears in the scientific report
2025
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