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Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies
Mike A. Nalls, Cornelis Blauwendraat, Costanza L. Vallerga, Karl Heilbron, Sara Bandrés‐Ciga, Diana Chang, Manuela Tan, Demis A. Kia, Alastair J. Noyce, Angli Xue, José Brás, Emily Young, Rainer von Coelln, Claudia Schulte, Manu Sharma, Lynne Krohn, Lasse Pihlstrøm, Ari Siitonen, Hampton L. Leonard, Faraz Faghri, Dena Hernández, Sonja W. Scholz, Juan A. Botía, María Martínez, Jean‐Christophe Corvol, Joseph Jankovic, Lisa M. Shulman, Margaret Sutherland, Pentti J. Tienari, Kari Majamaa, Mathias Toft, Ole A. Andreassen, Tushar Bangale, Alexis Brice, Jian Yang, Ziv Gan‐Or, Thomas Gasser, Joshua Shulman, Nicholas Wood, David A. Hinds, John Hardy, Peter M. Visscher, Robert Graham, Astrid Adarmes‐Gómez, Miquel Aguilar, Akbota Aitkulova, Vadim Akhmetzhanov, Roy N. Alcalay, Ignacio Álvarez, Victoria Álvarez, Francisco Javier Barrero, Jesús Alberto Bergareche Yarza, Inmaculada Bernal‐Bernal, Kimberley J. Billingsley, Marta Bonilla‐Toribio, María Teresa Boungiorno, Kathrin Brockmann, Vivien J. Bubb, Dolores Buiza‐Rueda, Anna Maria Novella Càmara, Fátima Carrillo, Mario Carrión‐Claro, Debora Cerdan, Viorica Chelban, Jordi Clarimón, Carl E Clarke, Yaroslau Compta, Mark Cookson, David W. Craig, Fabrice Danjou, Mónica Díez-Fairén, Oriol Dols‐Icardo, J. Duarte, Raquel Durán, Francisco Escamilla‐Sevilla, Valentina Escott‐Price, Mario Ezquerra, Cici Feliz, Manel Fernández, Rubén Fernández‐Santiago, Steven Finkbeiner, Thomas Foltynie, Ciara García, Pedro Ruiz, María José Gómez Heredia, Pilar Gómez‐Garre, Manuel Menéndez‐González, Isabel González Aramburu, Sebastian Guelfi, Rita Guerreiro, Sharon Hassin‐Baer, Janet Hoenicka, Peter Holmans, Henry Houlden, Jon Infante, Silvia Jesús, Adriano Jiménez‐Escrig, Gulnaz Kaishybayeva, Rauan Kaiyrzhanov, Altynay Karimova, Kerri J. Kinghorn, Sulev Kõks, Jaime Kulisevsky, Miguel A. Labrador‐Espinosa, Patrick A. Lewis, José Luis López-Sendón, Ruth C. Lovering, Steven Lubbe, Codrin Lungu, Daniel Macías, Claudia Manzoni, Juan Marín‐Lahoz, Johan Marinus, Marı́a José Martı́, Irene Martínez‐Torres, Juan Carlos Martínez‐Castrillo, Marina Mata, Niccolò E. Mencacci, Carlota Méndez‐del‐Barrio, Ben Middlehurst, Adolfo Mínguez‐Castellanos, Pablo Mir, Kin Y. Mok, Esteban Muñoz, Derek P. Narendra, Oluwadamilola O. Ojo, Njideka Okubadejo, Ana Gorostidi Pagola, Pau Pástor, Francisco Pérez Errazquin, María Teresa Periñán, Hélène Plun‐Favreau, John P. Quinn, Lea R’Bibo, Xylena Reed, Elisabet Mondragón Rezola, Mie Rizig, Patrizia Rizzu, Laurie Robak, A Rodríguez, Guy A. Rouleau, Javier Ruiz‐Martínez, Clara Ruz, Mina Ryten, Dinara Sadykova, Sebastian R. Schreglmann, Chingiz Shashkin, María Sierra, Esther Suárez-Sanmartín, Pille Taba, César Tabernero, Manuela X Tan, Juan Pablo Tartari, Cristina Tejera‐Parrado, Eduard Tolosa, Daniah Trabzuni, Francesc Valldeoriola, Jacobus J. van Hilten, Kendall Van Keuren‐Jensen, Laura Vargas‐González, Lydia Vela, Francisco Vives, Nigel Williams, Nazira Zharkinbekova, Elena Zholdybayeva, Alexander Zimprich, Pauli Ylikotila, Stephen G. Reich, Joseph M. Savitt, Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, Karen E. Huber, Barry Hicks, Ethan M. Jewett, Yunxuan Jiang, Aaron Kleinman, Keng‐Han Lin, Nadia K. Litterman, Jennifer C. McCreight, Matthew H. McIntyre, Kimberly F. McManus, Joanna L. Mountain, Elizabeth S. Noblin, Carrie A. M. Northover, Steven J. Pitts, G. David Poznik, J. Fah Sathirapongsasuti, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic, Xin Wang, Catherine H. Wilson, Tim Anderson, Steven R. Bentley, John C. Dalrymple‐Alford, Javed Fowdar, Glenda M. Halliday, Anjali K. Henders, Ian B. Hickie, Irfahan Kassam, Martin A. Kennedy, John B. Kwok, Simon J.G. Lewis, George D. Mellick, Grant W. Montgomery, John F. Pearson, Toni L. Pitcher, Julia Sidorenko, Peter A. Silburn, Leanne Wallace, Naomi R. Wray, Futao Zhang
Bibliographic record
VenueThe Lancet Neurology · 2019
Typereview
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersDivision of Human Resource ManagementNational Institute on AgingMedical Research CouncilSchool of Public Health, University of California BerkeleyFédération pour la Recherche sur le CerveauNorges ForskningsrådAgence Nationale de la RechercheChung Hua UniversityObstetric Anaesthetists' AssociationBiogenLondon Mathematical SocietyParkinson's UKNovartisPSP AssociationAdrienne Helis Malvin Medical Research FoundationGE HealthcareNorth Carolina GlaxoSmithKline FoundationNational Institutes of HealthRosetrees TrustAssociation France ParkinsonEuropean CommissionSanofiBarts CharityBoehringer IngelheimMichael J. Fox Foundation for Parkinson's ResearchRocheInstitut de FranceFondation Roger de SpoelberchH. Lundbeck A/SBurroughs Wellcome Fund
KeywordsGenome-wide association studyDiseaseLRRK2Genetic associationSingle-nucleotide polymorphismMendelian randomizationGeneticsBiologyMeta-analysisMendelian inheritanceHeritabilityMissing heritability problemParkinson's diseaseBioinformaticsMedicineGenotypeGeneGenetic variantsInternal medicine
Abstract
No abstract in any covered source. Its absence is recorded, not treated as a negative.
No abstract. This is not a gap in this database; OpenAlex has none either. 23.3% of the frame is in this state, and the screen finds HALF as much metaresearch here, so the absence is a measured bias rather than a missing field.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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)0.010
metaresearch head score (Gemma)0.014
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.010
Threshold uncertainty score0.051
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.014 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.014 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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 head0.132
GPT teacher head0.362
Teacher spread0.229 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine 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 designMeta-analysis
Domainnot available
GenreReview
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
Citations2,541
Published2019
Admission routes1
Has abstractno