Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Genetics
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To (1) validate past results by investigating the role of LRRK2 exonic variants in an equivalent Korean series with MSA and (2) identify novel associations with LRRK2 and MSA in the Korean population.
Background: Multiple system atrophy (MSA) is a rare, sporadic, adult-onset neurodegenerative disorder that is similar both clinically and pathologically to Parkinson’s disease (PD). MSA is characterized by rapidly progressive autonomic dysfunction along with Parkinsonian features (MSA-P subtype) or cerebellar features (MSA-C subtype). Mutations in the LRRK2 gene are known to be one of the most common genetic causes of PD to date. Variants in LRRK2 have been previously associated with PD susceptibility in both Caucasian and Asian PD patients. Recently, an inversely-associated haplotype in LRRK2 was reported in a Caucasian MSA cohort.
Methods: We evaluated the association between common LRRK2 exonic variants and MSA in the Korean population. Thirteen SNPs selected from previous LRRK2 MSA and PD studies were genotyped in 759 MSA patients and 463 controls. Nominal SNP and haplotype associations were assessed using logistic regression models.
Results: Trends towards risk associations were observed for rs7308720 (N551K), rs7133914 (R1398H), and rs11175964 (K1423K) before multiple testing correction. The inversely-associated haplotype reported by Ross et al. (Lancet Neurol., 2011, 10:898-908) was also identified in our study, but was not significant after multiple testing correction. Further haplotype analyses led to the identification of a novel haplotype spanning a large portion of LRRK2 associated with risk for MSA (OR = 1.39; 95% CI = 1.16-1.67; p = 0.013).
Conclusions: Our study replicates, in the Korean population, the associations observed between LRRK2 and MSA and also reports a novel risk haplotype. Within this novel haplotype, we hypothesize the associated region lies at rs7133914. We suggest that rs7133914 on its own, or together with another variant in trans, affects LRRK2 GTPase activity to ultimately perturb protein function. Our results further implicate LRRK2 in the pathogenesis of MSA and point to LRRK2 GTPase function as a potential therapeutic target.
(Poster) American Society of Human Genetics Annual Meeting, October 6-10 2015, Baltimore (USA).
To cite this abstract in AMA style:
L.L. Farrell, E. Scott, H.J. Kim, I. Guella, S. Bortnick, E.M. Nosova, B. Jeon, C.W. Sin, H. Park, S.S. Park, M.J. Farrer. A novel haplotype in LRRK2 is associated with risk for multiple system atrophy in the Korean population [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/a-novel-haplotype-in-lrrk2-is-associated-with-risk-for-multiple-system-atrophy-in-the-korean-population/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-novel-haplotype-in-lrrk2-is-associated-with-risk-for-multiple-system-atrophy-in-the-korean-population/