Objective: To investigate the prevalence of LRRK2 polymorphisms, R1628P and G2019S, and their association with Parkinson’s Disease (PD) in cohorts of East Asian (EA), Southeast Asian (SEA), and European descent (White).

Background: Risk loci are often examined by genome-wide association study (GWAS) analysis in populations who self-identify as White, leaving other groups underrepresented[1] . G2019S is a prevalent LRRK2 polymorphism in White populations, but R1628P is a major risk factor for PD in Asian populations [2,3]. However, most Asian cohorts are predominantly EA [4] and SEA remain underrepresented [5,6]. We aim to explore differences in LRRK2 risk loci between cohorts of White, EA, and SEA ancestry.

Method: Data was collected from five public genetic databases [8]: the All of Us Research Program, a study of Vietnamese patients with PD[7], a study of Chinese and non-Chinese Asians with PD[3], and two studies on LRRK2 variant distribution in PD populations[9,10]. Chi-square and odds ratios were used to observe associations of R1628P and G2019S with White, EA, and SEA ancestry and with PD diagnosis. Participants were grouped as: White, EA, or SEA with/without R1628P/G2019S.

Results: Polymorphism prevalence by ethnicity is presented in table 1. PD diagnosis was not associated with R1628P in White participants (p = 0.382), but was among SEA (OR=2.50; p<.001) and EA (OR=2.65; p<.001) participants. PD diagnosis was associated with G2019S among White (OR=22.6; p<.001) and EA (OR=24.1; p=0.04), but not SEA, participants (p=0.880) (Table 2). White participants were less likely than EA/SEA to have R1628P (OR=0.20; p<.001) and more likely to have G2019S in general (OR=7.04; p<.001), but the prevalence of G2019S amongst PD patients was similar across all ethnicities. There was no significant difference in the prevalence of R1628P (p=0.34) or G2019S (p=0.43) between SEA/EA (Tables 3 & 4).

Conclusion: R1628P was associated with a higher likelihood of PD in EA and SEA, but not White, participants while G2019S was associated with a higher likelihood of PD in White and EA, but not SEA, participants. This highlights the differences in the risk allele effect of polymorphisms across populations and the need for global genetic studies to assess the prevalence and penetrance of polymorphisms in PD.

Table 1

Table 2A-B

Table 2C and Table 3

Table 4

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3. Zhang, Y., Sun, Q., Yi, M., Zhou, X., Guo, J., Xu, Q., Tang, B., & Yan, X. (2017). Genetic Analysis of LRRK2 R1628P in Parkinson’s Disease in Asian Populations. Parkinson’s Disease, 2017(1), 8093124. https://doi.org/10.1155/2017/8093124

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lrrk2-polymorphisms-and-associations-with-parkinsons-disease-in-participants-of-east-asian-southeast-asian-and-european-descent/