The Landscape of Monogenic Parkinson’s Disease in Populations of Non-European Ancestry: A Narrative Review

Abstract

Introduction: There has been a bias in the existing literature on Parkinson’s disease (PD) genetics as most studies involved patients of European ancestry, mostly in Europe and North America. Our target was to review published research data on the genetic profile of PD patients of non-European or mixed ancestry. Methods: We reviewed articles published during the 2000–2023 period, focusing on the genetic status of PD patients of non-European origin (Indian, East and Central Asian, Latin American, sub-Saharan African and Pacific islands). Results: There were substantial differences regarding monogenic PD forms between patients of European and non-European ancestry. The G2019S Leucine Rich Repeat Kinase 2 (LRRK2) mutation was rather scarce in non-European populations. In contrast, East Asian patients carried different mutations like p.I2020T, which is common in Japan. Parkin (PRKN) variants had a global distribution, being common in early-onset PD in Indians, in East Asians, and in early-onset Mexicans. Furthermore, they were occasionally present in Black African PD patients. PTEN-induced kinase 1 (PINK1) and PD protein 7 (DJ-1) variants were described in Indian, East Asian and Pacific Islands populations. Glucocerebrosidase gene variants (GBA1), which represent an important predisposing factor for PD, were found in East and Southeast Asian and Indian populations. Different GBA1 variants have been reported in Black African populations and Latin Americans. Conclusions: Existing data reveal a pronounced heterogeneity in the genetic background of PD. A number of common variants in populations of European ancestry appeared to be absent or scarce in patients of diverse ethnic backgrounds. Large-scale studies that include genetic screening in African, Asian or Latin American populations are underway. The outcomes of such efforts will facilitate further clinical studies and will possibly contribute to the identification of either new pathogenic mutations in already described genes or novel PD-related genes.

Towards a Global View of Parkinson's Disease Genetics

“…82 In contrast, pathogenic variants in the SNCA gene have not been frequently reported as a cause of PD in Latin American people. 83 Even so, the prevalence of SNCA mutations in the general population is very rare, and the penetrance is variable. 84 Although most of the reported carriers develop the disease before the age of 50 years, some individuals with duplications may persist as asymptomatic even into older age.…”

“…90,91 Although other potential disease-causing variants have been reported, only the p.D620N variant has been definitively classified as pathogenic. 51 A small number of studies including VPS35 have been conducted in underrepresented populations and mainly focus on specific mutations such as p.D620N and p.R524W, 83 making it more challenging to confirm the pathogenicity of less-studied variants in these groups. Penetrance studies of the VPS35 p.D620N mutation show that 25% of carriers manifest PD by the age of ≤45 years; the median age of onset is 49 years, and 75% of individuals develop symptoms by the age of ≥59 years.…”