Objective: We aimed to review existing literature on the genetic background of Parkinson’s disease (PD) populations of non-Caucasian or mixed ancestry.

Background: There has been a systematic bias in former research on PD genetics as the vast majority of studies have focused on populations of Caucasian ancestry mostly in Europe and North America.

Method: We reviewed articles in Pubmed spanning the 2000-2021 period, with a focus on genetic data in PD patients of non-Caucasian origin (East and Central Asian, Indian, sub-Saharan African and Latin American).

Results: Pathogenic alpha-synuclein (SNCA) variants were very sparse or absent in most non-Caucasian populations. The G2019S Leucine Rich Repeat Kinase 2 (LRRK2) variant (common in patients of European and Ashkenazi Jewish /Northern African descent) was very rare in other populations with the exception of Central Asian. In contrast, East Asian patients harbored different variants like the G2385A. LRRK2 mutations were rare in Indian and in Black African population studies. Latin American populations of indigenous origin harbored the LRRK2 K198E.
Parkin (PRKN) variants appeared to have a global distribution. They were particularly common in young-onset PD in East Asians and Indians. PRKN carriers were also found among Black African PD patients and early-onset Mexicans. PTEN-induced kinase 1 (PINK1) and PD protein 7 (DJ-1) were reported in East Asian (China, Korea), Indian and Sub Sahara African PD cases.
Glucocerebrosidase gene variants (GBA) as a risk factor for PD were found in Asian cases [China, Taiwan, Korea, Malaysia and Thailand (mainly the p.L444P variant but rarely the N370S)]. Indian population studies of screening for GBA were contradictory (with p.L444P being the commonest). GBA variants were occasionally reported in Black African populations and Latin Americans. Variants in other rarer genes have been published in East Asian studies including ATP13A2, PLA2G6 and CHCHD2.

Conclusion: Accumulating data suggest that there is a marked heterogeneity in the genetic landscape of PD with many common variants in Caucasian-ancestry populations being absent or very rare in patients of different backgrounds. Large-scale genetic screening efforts in Asian, African or Latin American populations which are ongoing will inform clinical studies and will possibly pave the way for the discovery of either new pathogenic variants in existing genes or novel PD-related genes.

References: [1] Lim SY, Tan AH, Ahmad-Annuar A, Klein C, Tan LCS, Rosales RL, Bhidayasiri R, Wu YR, Shang HF, Evans AH, Pal PK, Hattori N, Tan CT, Jeon B, Tan EK, Lang AE. Parkinson’s disease in the Western Pacific Region. Lancet Neurol. 2019 Sep;18(9):865-879.
[2] Zhao Y, Qin L, Pan H, Liu Z, Jiang L, He Y, Zeng Q, et al. The role of genetics in Parkinson’s disease: a large cohort study in Chinese mainland population. Brain. 2020 Jul 1;143(7):2220-2234.
[3] Dekker MCJ, Coulibaly T, Bardien S, Ross OA, Carr J, Komolafe M. Parkinson’s Disease Research on the African Continent: Obstacles and Opportunities. Front Neurol. 2020 Jun 19;11:512.
[4] Sarihan EI, Pérez-Palma E, Niestroj LM, Loesch D, Inca-Martinez M, Horimoto ARVR, Cornejo-Olivas M, et al. Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD)‡. Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson’s Disease Patients. Mov Disord. 2021 Feb;36(2):434-441.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-genetic-landscape-of-parkinsons-disease-in-populations-of-non-caucasian-ancestry/