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Record W4416915850 · doi:10.1038/s41531-025-01180-z

TMEM175, SCARB2 and CTSB associations with Parkinson’s disease risk across populations

2025· article· en· W4416915850 on OpenAlexaff
Wen-Hua Sun, Claudia Schulte, Thomas Gasser, Manuela Tan, 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, 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, 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, Ai Huey Tan, Azlina Ahmad‐Annuar, Shen‐Yang Lim, Yi Wen Tay, Shahrul Azmin, Nor Azian Abdul Murad, Daniel Martínez-Ramírez, Mayela Rodríguez‐Violante, Paula Reyes‐Pérez, Bayasgalan Tserensodnom, Rajeev Ojha, Tim Anderson, Toni L. Pitcher, Oluwadamilola O. Ojo, Jan Aasly, Shoaib Ur-Rehman, Mario Cornejo‐Olivas, Maria Leila M. Doquenia, Raymond L. Rosales, Ángel Viñuela, Е. А. Яковенко, Bashayer Al Mubarak, Muhammad Umair, Eng‐King Tan, Ferzana Amod, Jonathan Carr, Soraya Bardien, Beomseok Jeon, Yun Joong Kim, Esther Cubo, Ignacio Álvarez, Janet Hoenicka, Katrin Beyer, Sarah El-Sadig, Christiane Zweier, Paul Krack, Chin‐Hsien Lin, Ruey‐Meei Wu, Hsiu-Chuan Wu, Yih‐Ru Wu, Pin‐Jui Kung, Serena Wu, Rim Amouri, Samia Ben Sassi, A. Nazl Başak, Özgür Öztop Çakmak, Sibel Ertan, Gençer Genç, Alejandro Martínez-Carrasco, Anette Schrag, Anthony H.V. Schapira, Eleanor J. Stafford, Henry Houlden, Huw R. Morris, John Hardy, Nicholas Wood, Olaitan Okunoye, Rauan Kaiyrzhanov, Rimona S. Weil, Simona Jasaitye, Vida Obese, Camille Carroll, Claire Bale, Donald G. Grosset, Kin Y. Mok, Nigel Williams, Patrick A. Lewis, Seth Love, Simon Stott, Alberto J. Espay, Luca Marsili, Alyssa O’Grady, Bernadette Siddiqi, Bradford Casey, Brian P. Fiske, Charisse Comart, J Solle, Kaileigh Murphy, Maggie Kuhl, Naomi Louie, Sohini Chowdhury, Todd Sherer, Andrew K. Sobering, Cabell Jonas, Carlos Cruchaga, Caroline B. Pantazis, Claire Wegel, Deborah J. Hall, Ejaz A. Shamim, Jared Williamson, Ekemini Riley, Sonya B. Dumanis, Geidy E. Serrano, Thomas G. Beach, Honglei Chen, Ignacio Juan Keller Sarmiento, Niccolò E. Mencacci, Steven Lubbe, Joseph Jankovic, Miguel Inca‐Martinez, Joshua Shulman, Karen Nuytemans, Karl Kieburtz, Katerina Markopoulou, Kenneth Marek, Lana M. Chahine, Lauren Ruffrage, Marissa Dean, Lisa Shulman, Roger L. Albin, Roy N. Alcalay, Ruth Walker, Tao Xie, Tatiana Foroud, Duan Nguyen, Toan Nguyen, Masharip Atadzhanov

Bibliographic record

Venuenpj Parkinson s Disease · 2025
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsMcGill University
FundersInstitut National Du CancerChina Scholarship CouncilMichael J. Fox Foundation for Parkinson's Research
KeywordsGenetic associationDiseaseGenome-wide association studyMissense mutationGenetic variantsGenetic testingGenetic variationAssociation testAssociation (psychology)

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.020
GPT teacher head0.308
Teacher spread0.287 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2025
Admission routes1
Has abstractyes

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