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Record W4408838016 · doi:10.1038/s41531-025-00896-2

The LRRK2 p.L1795F variant causes Parkinson’s disease in the European population

2025· article· en· W4408838016 on OpenAlexaff
Lara M. Lange, Kristin Levine, Susan H. Fox, Connie Marras, Nicole Kuznetsov, Dan Vitale, Hirotaka Iwaki, Katja Lohmann, Luca Marsili, Alberto J. Espay, Peter Bauer, Christian Beetz, Jessica Martin, Stewart A. Factor, Lenora A. Higginbotham, Honglei Chen, Hampton L. Leonard, Mike A. Nalls, Niccolò E. Mencacci, Huw R. Morris, Andrew Singleton, Christine Klein, Cornelis Blauwendraat, Zih‐Hua Fang, Emilia Gatto, Marcelo Kauffman, Samson Khachatryan, Zaruhi Tavadyan, Claire E. Shepherd, Julie Hunter, Kishore R. Kumar, Melina Ellis, Miguel E. Rentería, Sulev Kõks, Alexander Zimprich, Artur Francisco Schumacher Schuh, Carlos Roberto de Mello Rieder, Paula Saffie Awad, Vítor Tumas, Sarah Camargos, Edward A. Fon, Oury Monchi, Ted Fon, Benjamin Pizarro Galleguillos, Patricio Olguı́n, Marcelo Miranda, M. Leonor Bustamante, Pedro Chaná, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Gonzálo Arboleda, Jorge Orozco, Marlene Jiménez-Del-Río, Alvaro Hernández‐Flores, Mohamed Salama, Walaa A. Kamel, Yared Z. Zewde, Alexis Brice, Jean‐Christophe Corvol, Ana Westenberger, Eva‐Juliane Vollstedt, Harutyun Madoev, Joanne Trinh, Johanna Junker, Anastasia Illarionova, Brit Mollenhauer, Franziska Hopfner, Günter U. Höglinger, Manu Sharma, Thomas Gasser, Sergiu Groppa, Albert Akpalu, Georgia Xiromerisiou, Georgios Hadjigorgiou, Efthymios Dadiotis, 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, Divya KP, Pramod Pal, Prashanth Lingappa Kukkle, Roopa Rajan, Rupam Borgohain, Mehri Salari, Andrea Quattrone, Monica Gagliardi, Enza Maria Valente, Micol Avenali, Grazia Annesi, 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, Nor Azian Abdul Murad, Shahrul Azmin, Wael Mohamed, Daniel Martínez-Ramírez, Mayela Rodríguez‐Violante, Paula Reyes‐Pérez, Bayasgalan Tserensodnom, Rajeev Ojha, Tim Anderson, Toni L. Pitcher, Arinola Sanyaolu, Njideka Okubadejo, Oluwadamilola O. Ojo, Jan Aasly, Lasse Pihlstrøm, Manuela Tan, 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, Jia Nee Foo, Ferzana Amod, Jonathan Carr, Soraya Bardien, Beomseok Jeon, Yun Joong Kim, Esther Cubo, Ignacio Álvarez, Janet Hoenicka, Katrin Beyer, María Teresa Periñán, Pau Pástor, Sarah El-Sadig, Kajsa Brolin, Christiane Zweier, Paul Krack, Gerd Tinkhauser, Chin‐Hsien Lin, Pin‐Jui Kung, Hsiu-Chuan Wu, Ruey‐Meei Wu, Yih‐Ru Wu, Rim Amouri, Samia Ben Sassi, A. Nazlı Başak, Özgür Öztop Çakmak, Sibel Ertan, Gençer Genç, Alastair J. Noyce, Sumit Dey, Alejandro Martínez-Carrasco, Anette Schrag, Anthony H.V. Schapira, Eleanor J. Stafford, Henry Houlden, John Hardy, Kin Y. Mok, Mie Rizig, Nicholas Wood, Olaitan Okunoye, Rauan Kaiyrzhanov, Rimona S. Weil, Simona Jasaityte, Vida Obese, Camille Carroll, Claire Bale, Donald G. Grosset, Nigel Williams, Patrick A. Lewis, Seth Love, Simon Stott, Caroline B. Pantazis, Laurel Screven, Sara Bandrés‐Ciga, Ignacio Juan Keller Sarmiento, Alyssa O’Grady, Bernadette Siddiqi, Bradford Casey, Brian Fiske, Charisse Comart, J Solle, Kaileigh Murphy, Maggie Kuhl, Naomi Louie, Sohini Chowdhury, Todd Sherer, Andrew K. Sobering, Cabell Jonas, Carlos Cruchaga, Laura Ibáñez, Claire Wegel, Tatiana Foroud, Deborah A. Hall, Dena G. Hernandez, Jonggeol Jeff Kim, Yeajin Song, Ejaz Shiamim, Ekemini Riley, Geidy E. Serrano, Ignácio F. Mata, Miguel Inca‐Martinez, Jared Williamson, Joseph Jankovic, Joshua Shulman, Kamalini Ghosh Galvelis, Karen Nuytemans, Karl Kieburtz, Katerina Markopoulou, Kenneth Marek, Lana M. Chahine, Lauren Ruffrage, Lisa Shulman, Marissa Dean, Matthew J. Farrer, Megan J. Puckelwartz, Steven Lubbe, Roger L. Albin, Roy N. Alcalay, Ruth Walker, Sonya B. Dumanis, Tao Xie, Thomas Beach, Faraz Faghri, Mary B. Makarious, Mathew J. Koretsky, Duan Nguyen, Toan Nguyen, Masharip Atadzhanov

Bibliographic record

Venuenpj Parkinson s Disease · 2025
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsMcGill UniversityToronto Western HospitalInstitut Universitaire de Gériatrie de MontréalMontreal Neurological Institute and HospitalUniversity of TorontoUniversity Health Network
FundersParkinsonfondenH. Lundbeck A/SNational Institute of Neurological Disorders and StrokeVerily Life SciencesAcorda TherapeuticsMedical Research CouncilBiogenCelgeneParkinson's UKCHDI FoundationSanofiGlaxoSmithKlineParkinson's FoundationPfizerBristol-Myers SquibbMichael J. Fox Foundation for Parkinson's ResearchUniversity of CambridgeBoston Scientific CorporationNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsLRRK2Parkinson's diseaseDiseaseHaplotypeGenotypingGeneticsMedicineBiologyGenotypeInternal medicineGene

Abstract

fetched live from OpenAlex

LRRK2-PD represents the most common form of autosomal dominant Parkinson's disease. We identified the LRRK2 p.L1795F variant in three families and six additional unrelated cases using genetic data from over 50,000 individuals. Carriers with available genotyping data shared a common haplotype. The clinical presentation resembles other LRRK2-PD forms. Combined with published functional evidence showing strongly enhanced LRRK2 kinase activity, we provide evidence that LRRK2 p.L1795F is pathogenic.

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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
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 head0.017
GPT teacher head0.278
Teacher spread0.261 · 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

Citations3
Published2025
Admission routes1
Has abstractyes

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