medRxiv : the preprint server for health sciences · 2025
The LRRK2 p.A419V variant associates with risk of Parkinson's disease in the East Asian population and an evaluation on age of onset.
СтатьяПрепринтНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lim Kai Shi, Periñan Maria Teresa, Chew Elaine Guo Yan, Lee Paul Suhwan, Akçimen Fulya, Lim Jia Lun, Koretsky Mathew J, Funayama Manabu, Yoshino Hiroyo, Hattori Nobutaka, Kaiyrzhanov Rauan, Houlden Henry, Isayan Mariam, Tay Yi Wen, Toh Tzi Shin, Lit Lei-Cheng, Khairul Anuar Anis Nadhirah, Ding Hans Xing, Screven Laurel, Mohamed Ibrahim Norlinah, Lin Chin-Hsien, Kim Han-Joon, Lee Jee-Young, Chung Sun Ju, Foo Jia Nee, Tan Eng-King, Lim Shen-Yang, Tan Ai Huey, Bandres-Ciga Sara, Ahmad-Annuar Azlina, Global Parkinson’s Genetics Program (GP2)
Аннотация
Common and rare variants in LRRK2 influence Parkinson's disease (PD) risk across diverse populations. We investigated the p.A419V variant across multiple ancestry cohorts comprising over 200,000 individuals. In cases of East Asian ancestry, the variant was significantly associated with increased risk (OR = 2.9; 95% CI: 1.66-5.10; p = 0.0002), It lies on rare EAS haplotypes, and was not in linkage disequilibrium with other LRRK2 coding variants. Although not significant, meta-analysis of age of onset in EAS cases show a suggestive trend (β = -0.89 years; SE = 1.01; p = 0.380). LRRK2 protein modelling prediction indicated that binding sites for RAB8A, RAB10, RAB29 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 pathway.