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Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry.
Mov Disord. 2017 Oct; 32(10):1432-1438.MD

Abstract

BACKGROUND

Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24%-100%). The p.G2019S penetrance in individuals of Ashkenazi Jewish ancestry has been estimated as 25%, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non-Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non-Ashkenazi Jews to age 80.

METHODS

The kin-cohort method was used to estimate penetrance in 474 first-degree relatives of 69 non-Ashkenazi Jewish LRRK2 p.G2019S carrier probands at 8 sites from the Michael J. Fox LRRK2 Cohort Consortium. An identical validated family history interview was administered to assess age at onset of PD, current age, or age at death for relatives in different ethnic groups at each site. Neurological examination and LRRK2 genotype of relatives were included when available.

RESULTS

Risk of PD in non-Ashkenazi Jewish relatives who carry a LRRK2 p.G2019S mutation was 42.5% (95% confidence interval [CI]: 26.3%-65.8%) to age 80, which is not significantly higher than the previously estimated 25% (95% CI: 16.7%-34.2%) in Ashkenazi Jewish carrier relatives. The penetrance of PD to age 80 in LRRK2 p.G2019S mutation carrier relatives was significantly higher than the noncarrier relatives, as seen in Ashkenazi Jewish relatives.

CONCLUSIONS

The similar penetrance of LRRK2 p.G2019S estimated in Ashkenazi Jewish carriers and non-Ashkenazi Jewish carriers confirms that p.G2019S penetrance is 25% to 42.5% at age 80 in all populations analyzed. © 2017 International Parkinson and Movement Disorder Society.

Authors+Show Affiliations

Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York, USA.Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York, USA.Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.Department of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA.Department of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA.Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ) Paris 06. Institut National de la Santé et de la Recherche Médicale, U1127, Paris, France. Centre National de la Recherche Scientifique, UMR 7225, Paris, France. Institut du Cerveau et de la Moelle Epinière (ICM), Hôpital Pitié-Salpêtrière, Département des maladies du système nerveux, F-75013, Paris, France. Department of Neurology, Institut National de la Santé et de la Recherche Médicale, Assistance-Publique Hôpitaux de Paris, CIC-1422, Hôpital Pitié-Salpêtrière, Paris, France. Assistance publique - Hôpitaux de Paris (AP-HP), 75015, Paris, France.Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ) Paris 06. Institut National de la Santé et de la Recherche Médicale, U1127, Paris, France. Centre National de la Recherche Scientifique, UMR 7225, Paris, France. Institut du Cerveau et de la Moelle Epinière (ICM), Hôpital Pitié-Salpêtrière, Département des maladies du système nerveux, F-75013, Paris, France. Department of Neurology, Institut National de la Santé et de la Recherche Médicale, Assistance-Publique Hôpitaux de Paris, CIC-1422, Hôpital Pitié-Salpêtrière, Paris, France. Assistance publique - Hôpitaux de Paris (AP-HP), 75015, Paris, France.Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ) Paris 06. Institut National de la Santé et de la Recherche Médicale, U1127, Paris, France. Centre National de la Recherche Scientifique, UMR 7225, Paris, France. Institut du Cerveau et de la Moelle Epinière (ICM), Hôpital Pitié-Salpêtrière, Département des maladies du système nerveux, F-75013, Paris, France. Department of Neurology, Institut National de la Santé et de la Recherche Médicale, Assistance-Publique Hôpitaux de Paris, CIC-1422, Hôpital Pitié-Salpêtrière, Paris, France. Assistance publique - Hôpitaux de Paris (AP-HP), 75015, Paris, France.Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ) Paris 06. Institut National de la Santé et de la Recherche Médicale, U1127, Paris, France. Centre National de la Recherche Scientifique, UMR 7225, Paris, France. Institut du Cerveau et de la Moelle Epinière (ICM), Hôpital Pitié-Salpêtrière, Département des maladies du système nerveux, F-75013, Paris, France. Department of Neurology, Institut National de la Santé et de la Recherche Médicale, Assistance-Publique Hôpitaux de Paris, CIC-1422, Hôpital Pitié-Salpêtrière, Paris, France. Assistance publique - Hôpitaux de Paris (AP-HP), 75015, Paris, France.Neurology Service, Parkinson's disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain. Institut d'Investigacions Biomèdiques August Pi iSunyer, Barcelona, Spain. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain.Neurology Service, Parkinson's disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain. Institut d'Investigacions Biomèdiques August Pi iSunyer, Barcelona, Spain.Neurology Service, Parkinson's disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain. Institut d'Investigacions Biomèdiques August Pi iSunyer, Barcelona, Spain.Parkinson's Institute and Clinical Center, Sunnyvale, California, USA.Parkinson's Institute and Clinical Center, Sunnyvale, California, USA.Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA.Department of Neurology, Christian-Albrechts-University of Kiel and Hertie-Institute of Clinical Brain Research, University of Tübingen, Germany.Department of Neurodegeneration, Hertie-Institute of Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Germany.Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) "Gaetano Pini-CTO", Milan, Italy.Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) "Gaetano Pini-CTO", Milan, Italy.Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy. Humanitas Clinical and Research Center, Milan, Italy.Department of Neurology, Donostia University Hospital, Biodonostia Research Institute, San Sebastián (Gipuzkoa), Spain. Centre for Networked Biomedical Research on Neurodegenerative Diseases, Madrid, Spain.Department of Neurology, Donostia University Hospital, Biodonostia Research Institute, San Sebastián (Gipuzkoa), Spain. Centre for Networked Biomedical Research on Neurodegenerative Diseases, Madrid, Spain.Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Research, Toronto, Canada.Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Research, Toronto, Canada.Sackler School of Medicine, Sagol School for Neurosciences, Tel Aviv University, Tel Aviv, Israel. Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.Sackler School of Medicine, Sagol School for Neurosciences, Tel Aviv University, Tel Aviv, Israel. Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28639421

Citation

Lee, Annie J., et al. "Penetrance Estimate of LRRK2 p.G2019S Mutation in Individuals of non-Ashkenazi Jewish Ancestry." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 32, no. 10, 2017, pp. 1432-1438.
Lee AJ, Wang Y, Alcalay RN, et al. Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry. Mov Disord. 2017;32(10):1432-1438.
Lee, A. J., Wang, Y., Alcalay, R. N., Mejia-Santana, H., Saunders-Pullman, R., Bressman, S., Corvol, J. C., Brice, A., Lesage, S., Mangone, G., Tolosa, E., Pont-Sunyer, C., Vilas, D., Schüle, B., Kausar, F., Foroud, T., Berg, D., Brockmann, K., Goldwurm, S., ... Marder, K. (2017). Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry. Movement Disorders : Official Journal of the Movement Disorder Society, 32(10), 1432-1438. https://doi.org/10.1002/mds.27059
Lee AJ, et al. Penetrance Estimate of LRRK2 p.G2019S Mutation in Individuals of non-Ashkenazi Jewish Ancestry. Mov Disord. 2017;32(10):1432-1438. PubMed PMID: 28639421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry. AU - Lee,Annie J, AU - Wang,Yuanjia, AU - Alcalay,Roy N, AU - Mejia-Santana,Helen, AU - Saunders-Pullman,Rachel, AU - Bressman,Susan, AU - Corvol,Jean-Christophe, AU - Brice,Alexis, AU - Lesage,Suzanne, AU - Mangone,Graziella, AU - Tolosa,Eduardo, AU - Pont-Sunyer,Claustre, AU - Vilas,Dolores, AU - Schüle,Birgitt, AU - Kausar,Farah, AU - Foroud,Tatiana, AU - Berg,Daniela, AU - Brockmann,Kathrin, AU - Goldwurm,Stefano, AU - Siri,Chiara, AU - Asselta,Rosanna, AU - Ruiz-Martinez,Javier, AU - Mondragón,Elisabet, AU - Marras,Connie, AU - Ghate,Taneera, AU - Giladi,Nir, AU - Mirelman,Anat, AU - Marder,Karen, AU - ,, Y1 - 2017/06/22/ PY - 2016/12/14/received PY - 2017/05/05/revised PY - 2017/05/07/accepted PY - 2017/6/24/pubmed PY - 2018/6/13/medline PY - 2017/6/23/entrez KW - LRRK2 KW - Parkinson's disease KW - penetrance SP - 1432 EP - 1438 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov. Disord. VL - 32 IS - 10 N2 - BACKGROUND: Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24%-100%). The p.G2019S penetrance in individuals of Ashkenazi Jewish ancestry has been estimated as 25%, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non-Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non-Ashkenazi Jews to age 80. METHODS: The kin-cohort method was used to estimate penetrance in 474 first-degree relatives of 69 non-Ashkenazi Jewish LRRK2 p.G2019S carrier probands at 8 sites from the Michael J. Fox LRRK2 Cohort Consortium. An identical validated family history interview was administered to assess age at onset of PD, current age, or age at death for relatives in different ethnic groups at each site. Neurological examination and LRRK2 genotype of relatives were included when available. RESULTS: Risk of PD in non-Ashkenazi Jewish relatives who carry a LRRK2 p.G2019S mutation was 42.5% (95% confidence interval [CI]: 26.3%-65.8%) to age 80, which is not significantly higher than the previously estimated 25% (95% CI: 16.7%-34.2%) in Ashkenazi Jewish carrier relatives. The penetrance of PD to age 80 in LRRK2 p.G2019S mutation carrier relatives was significantly higher than the noncarrier relatives, as seen in Ashkenazi Jewish relatives. CONCLUSIONS: The similar penetrance of LRRK2 p.G2019S estimated in Ashkenazi Jewish carriers and non-Ashkenazi Jewish carriers confirms that p.G2019S penetrance is 25% to 42.5% at age 80 in all populations analyzed. © 2017 International Parkinson and Movement Disorder Society. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/28639421/Penetrance_estimate_of_LRRK2_p_G2019S_mutation_in_individuals_of_non_Ashkenazi_Jewish_ancestry_ L2 - https://doi.org/10.1002/mds.27059 DB - PRIME DP - Unbound Medicine ER -