LRRK2 p.G2385R and p.R1628P variants in a multi-ethnic Asian Parkinson’s Cohort: epidemiology and clinical insights

TY - JOUR

T1 - LRRK2 p.G2385R and p.R1628P variants in a multi-ethnic Asian Parkinson’s Cohort

T2 - epidemiology and clinical insights

AU - Goh, Jun Wen

AU - Lim, Jia Lun

AU - Toh, Tzi Shin

AU - Ong, Rui Yan

AU - Yong, Qing Hui

AU - Lew, Cindy Choey Yee

AU - Hor, Jia Wei

AU - Tay, Yi Wen

AU - Zulkefli, Jannah

AU - Khairul Anuar, Anis Nadhirah

AU - Ding, Hans Xing

AU - Schee, Jie Ping

AU - Beh, Yuan Ye

AU - Ibrahim, Khairul Azmi

AU - Mawardi, Ahmad Shahir

AU - Lim, Thien Thien

AU - Looi, Irene

AU - Chia, Yuen Kang

AU - Ooi, Joshua Chin Ern

AU - Law, Wan Chung

AU - Wong, Siaw Cheng

AU - Lau, Yue Hui

AU - Teh, Pei Chiek

AU - Ong, Tien Lee

AU - Cheah, Wee Kooi

AU - Sammler, Esther

AU - Padmanabhan, Shalini

AU - Lit, Lei Cheng

AU - Tan, Eng King

AU - Ahmad-Annuar, Azlina

AU - Lim, Shen Yang

AU - Tan, Ai Huey

N1 - Publisher Copyright: © The Author(s) 2025.

PY - 2025/12

Y1 - 2025/12

N2 - The frequency and clinical impact of LRRK2 p.G2385R and p.R1628P risk variants in Parkinson’s disease (PD) remain uncertain, particularly across different Asian populations. We genotyped 3058 multi-ethnic Malaysian PD patients, performed detailed phenotyping in 185, and analyzed disease progression in 635 using longitudinal Clinical Impression of Severity Index for PD scores. p.G2385R was largely confined to Chinese (8.2%), while p.R1628P occurred in mixed ancestry (11.0%), Chinese (8.3%), Malays (7.7%), and is reported for the first time in indigenous groups (3.9%). Double-variant carriers had younger onset and more frequently had positive family history. Compared with non-carriers, p.R1628P carriers had lower rates of dementia and orthostatic hypotension, and slower progression of global PD severity. Our findings highlight ethnic differences in the distribution of LRRK2 Asian variants, and suggest that these variants influence onset age, familial occurrence, non-motor features, and disease course, with implications for personalized approaches to PD in Asian populations.

AB - The frequency and clinical impact of LRRK2 p.G2385R and p.R1628P risk variants in Parkinson’s disease (PD) remain uncertain, particularly across different Asian populations. We genotyped 3058 multi-ethnic Malaysian PD patients, performed detailed phenotyping in 185, and analyzed disease progression in 635 using longitudinal Clinical Impression of Severity Index for PD scores. p.G2385R was largely confined to Chinese (8.2%), while p.R1628P occurred in mixed ancestry (11.0%), Chinese (8.3%), Malays (7.7%), and is reported for the first time in indigenous groups (3.9%). Double-variant carriers had younger onset and more frequently had positive family history. Compared with non-carriers, p.R1628P carriers had lower rates of dementia and orthostatic hypotension, and slower progression of global PD severity. Our findings highlight ethnic differences in the distribution of LRRK2 Asian variants, and suggest that these variants influence onset age, familial occurrence, non-motor features, and disease course, with implications for personalized approaches to PD in Asian populations.

UR - https://www.scopus.com/pages/publications/105022494885

U2 - 10.1038/s41531-025-01166-x

DO - 10.1038/s41531-025-01166-x

M3 - Article

C2 - 41253790

AN - SCOPUS:105022494885

SN - 2373-8057

VL - 11

JO - NPJ Parkinson's disease

JF - NPJ Parkinson's disease

M1 - 320

ER -