ArticleNeurology2015
Age-specific penetrance of LRRK2 G2019S in the Michael J. Fox Ashkenazi Jewish LRRK2 Consortium.
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Article in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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101 citing papers in PubMed, 166 citations in OpenAlex.
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- Multimodal Remote Digital Phenotyping for Detecting and Tracking Early Parkinsonian Change in LRRK2 Carriers.Research square · 2026Article
- Low-frequency genetic variants in GAK enhance Golgi function and protect against Parkinson's disease.medRxiv : the preprint server for health sciences · 2025Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- The modifying effect of mutant LRRK2 on mutant GBA1-associated Parkinson disease.Human molecular genetics · 2025Article
- Cyclic Alternating Pattern Dynamics in Individuals at Risk for Developing Parkinson's Disease.Annals of neurology · 2025Article
- In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson's disease.Brain : a journal of neurology · 2025Article
- Heartbeat signature for predicting motor and non-motor involvement among nonparkinsonian LRRK2 G2019S mutation carriers.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2025Article
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- The effect of polygenic risk score on PD risk and phenotype inJournal of Parkinson's disease · 2025Article
- Clinical features and progression of Parkinson's disease with LRRK2 variants: A prospective study.Annals of clinical and translational neurology · 2025Article
- TheScience translational medicine · 2024Article
- Parkinson's families project: a UK-wide study of early onset and familial Parkinson's disease.NPJ Parkinson's disease · 2024Article
- LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.Trends in molecular medicine · 2024Review
- TheResearch square · 2024Article
- Validity of the Short Weekly Calendar Planning Activity in patients with Parkinson disease and nonmanifesting LRRK2 and GBA carriers.European journal of neurology · 2024Article
- The Impact of LRRK2 G2019S on Parkinson's Disease: Clinical Phenotype and Treatment in Tunisian Patients.Journal of movement disorders · 2024Article
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Authors and funding
15 authors at 7 institutions in 2 countries.
Karen MarderFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel. ksm1@cumc.columbia.edu.
Yuanjia WangFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Roy N AlcalayFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Helen Mejia-SantanaFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Ming-Xin TangFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Annie LeeFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Deborah RaymondFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Anat MirelmanFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Rachel Saunders-PullmanFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Lorraine ClarkFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Laurie OzeliusFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Avi Orr-UrtregerFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Nir GiladiFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
Susan BressmanFrom the Departments of Neurology (K.M., R.N.A., H.M.-S., M.-X.T.) and Pathology and Cell Biology (L.C.), and Center for Human Genetics (L.C.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (K.M., R.N.A., M.-X.T., L.C.) and Department of Biostatistics, Mailman School of Public Health (Y.W., A.L.), Columbia University, New York; The Alan and Barbara Mirken Department of Neurology (D.R., R.S.-P., S.B.), Beth Israel Medical Center, New York, NY; Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center (A.M., N.G.), Sackler School of Medicine (A.O.U.), and Sagol School for Neurosciences (A.M., N.G.), Tel Aviv University; School of Health Related Professions (A.M.), Ben Gurion University, Beer Sheba, Israel; Departments of Genetics and Genomic Sciences and Neurology (L.O.), Mount Sinai School of Medicine, New York, NY; and Genetics Institute (A.O.U.), Tel Aviv Sourasky Medical Center, Israel.
LRRK2 Ashkenazi Jewish Consortium
Ben-Gurion University of the Negev · ILColumbia University · USCenter for Human Genetics · USMount Sinai Beth Israel · USBen Taub Hospital · USTel Aviv University · ILIcahn School of Medicine at Mount Sinai · US
Funding
GENETIC EPIDEMIOLOGY OF PARKINSONS DISEASER01NS036630 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MARDER, KAREN S · 1998 to 2008
$6.8MIdentifying Huntington's disease markers by modern statistical learning methods.U01NS082062 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI WANG, YUANJIA · 2014 to 2016
$1.1MGenetic Epidemiology of Parkinson's DiseaseR56NS036630 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MARDER, KAREN S · 2010 to 2010
$500kNINDS NIH HHS R01 NS036630NINDS NIH HHS R56 NS036630NINDS NIH HHS U01 NS082062
Abstract
objectiveEstimates of the penetrance of LRRK2 G2019S vary widely (24%-100%), reflective of differences in ascertainment, age, sex, ethnic group, and genetic and environmental modifiers.
methodsThe kin-cohort method was used to predict penetrance in 2,270 relatives of 474 Ashkenazi Jewish (AJ) Parkinson disease (PD) probands in the Michael J. Fox LRRK2 AJ Consortium in New York and Tel Aviv, Israel. Patients with PD were genotyped for the LRRK2 G2019S mutation and at least 7 founder GBA mutations. GBA mutation carriers were excluded. A validated family history interview, including age at onset of PD and current age or age at death for each first-degree relative, was administered. Neurologic examination and LRRK2 genotype of relatives were included when available.
resultsRisk of PD in relatives predicted to carry an LRRK2 G2019S mutation was 0.26 (95% confidence interval [CI] 0.18-0.36) to age 80 years, and was almost 3-fold higher than in relatives predicted to be noncarriers (hazard ratio [HR] 2.89, 95% CI 1.73-4.55, p < 0.001). The risk among predicted G2019S carrier male relatives (0.22, 95% CI 0.10-0.37) was similar to predicted carrier female relatives (0.29, 95% CI 0.18-0.40; HR male to female: 0.74, 95% CI 0.27-1.63, p = 0.44). In contrast, predicted noncarrier male relatives had a higher risk (0.15, 95% CI 0.11-0.20) than predicted noncarrier female relatives (0.07, 95% CI 0.04-0.10; HR male to female: 2.40, 95% CI 1.50-4.15, p < 0.001).
conclusionPenetrance of LRRK2 G2019S in AJ is only 26% and lower than reported in other ethnic groups. Further study of the genetic and environmental risk factors that influence G2019S penetrance is warranted.
Indexed as
PenetranceAgedAge FactorsCohort StudiesFemaleHumansJewsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MaleMiddle AgedParkinson DiseaseProtein Serine-Threonine KinasesLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanProtein Serine-Threonine Kinases
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