Evidence map›Paper›PMID 41629305›Full record

ArticleNPJ Parkinson's disease2026

Association of LRRK2 p.A419V with Parkinson's Disease in East Asians and analysis of age at onset.

Kai Shi Lim, Maria Teresa Periñan, Elaine Guo Yan Chew, Paul Suhwan Lee, Fulya Akçimen, Jia Lun Lim, Mathew J Koretsky, Manabu Funayama, Hiroyo Yoshino, Nobutaka Hattori and 21 more

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Article in NPJ Parkinson's disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

31 authors.

Kai Shi LimDepartment of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Maria Teresa PeriñanUnidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Sevilla, Seville, Spain.
Elaine Guo Yan ChewLee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore.
Paul Suhwan LeeCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Fulya AkçimenLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Jia Lun LimThe Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
Mathew J KoretskyCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Manabu FunayamaDepartment of Neurology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Hiroyo YoshinoResearch Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Nobutaka HattoriDepartment of Neurology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Rauan KaiyrzhanovDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK.
Henry HouldenDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK.
Mariam IsayanDepartment of Neurology and Neurosurgery, National Institute of Health, Yerevan, Armenia.
Yi Wen TayDepartment of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Tzi Shin TohDepartment of Medicine, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Lei-Cheng LitDepartment of Physiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Anis Nadhirah Khairul AnuarDepartment of Physiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Hans Xing DingDepartment of Physiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Laurel ScrevenThe Global Parkinson's Genetics Program (GP2), Bethesda, USA.
Norlinah Mohamed IbrahimDepartment of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Selangor, Malaysia.
Chin-Hsien LinDepartment of Neurology, National Taiwan University Hospital Taipei, Taipei, Taiwan.
Han-Joon KimDepartment of Neurology, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Jee-Young LeeDepartment of Neurology, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Sun Ju ChungDepartment of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Jia Nee FooLee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore.
Eng-King TanDuke-National University of Singapore Medical School, Singapore, Singapore; Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore.
Shen-Yang LimDepartment of Medicine, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Ai Huey TanDepartment of Medicine, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia. aihuey.tan@um.edu.my.
Sara Bandres-CigaCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. sara.bandresciga@nih.gov.
Azlina Ahmad-AnnuarDepartment of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia. azlina_aa@um.edu.my.
Global Parkinson’s Genetics Program (GP2)

Funding

Boston-Korea Innovative Research Project through the Korea Health Industry Development Institute(KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea Grant no. : RS-2024-00403047Global Parkinson's Genetics Program (GP2). GP2 is funded by the Aligning Science Across Parkinson's (ASAP) initiative GP2 PhD FellowshipMedical Research Council MR/S01165X/1, MR/S005021/1, G0601943Medical Research Council, United Kingdom MR/S01165X/1, MR/S005021/1, G0601943National Science and Technology Council Grant number: 114-2311-B-002-008Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant MOH-000207The Japan Society for the Promotion of Science (JSPS) KAKENHI; The Japan Science and Technology Agency (JST) Moonshot R&D Program; The Japan Agency for Medical Research and Development (AMED); Subsidies for Current Expenditures to Private Institutions of Higher Education from the Promotion and Mutual Aid Corporation for Private Schools of Japan, a subaward from Juntendo University Grant Number: 24H00068; Grant Number: JPMJMS2024-5; Grant Numbers: 25bm1423015h0003, 24ek0109677h0002, JP23dm0207070, and JP23dm0307101;
6 · The paper itself

Abstract

Common and rare variants in LRRK2 influence Parkinson's disease (PD) risk across diverse populations, and in this study, the rare p.A419V variant was investigated across multiple ancestry cohorts comprising over 200,000 PD cases and controls. In cases of East Asian (EAS) ancestry, p.A419V was significantly associated with increased risk of PD (OR = 2.9; 95% CI: 1.66-5.10; p = 0.0002), and was not in linkage disequilibrium with other LRRK2 coding variants. The variant was significantly associated with a lower age at PD onset in the study cohort, while a meta-analysis of the EAS cases indicated a similar, albeit non-significant trend. LRRK2 protein modelling prediction indicated that binding sites for RAB8A, RAB29 and RAB32 were in close proximity to the p.A419V variant within the ARM domain. Together, these findings confirm the p.A419V as a significant PD risk factor in EAS populations, as well as highlight disease-relevant variants in the ARM domain and the link with LRRK2-RAB signaling.

Identifiers

PMID41629305
PMCPMC12913921

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