A Global Perspective of GBA1-Related Parkinson’s Disease: A Narrative Review

Abstract

Parkinson’s disease (PD) is considered to be the second most prominent neurodegenerative disease and has a global prevalence. Glucocerebrosidase (GBA1) gene mutations represent a significant hereditary risk factor for the development of PD and have a profound impact on the motor and cognitive progression of the disease. The aim of this review is to summarize the literature data on the prevalence, type, and peculiarities of GBA1 mutations in populations of different ethnic backgrounds. We reviewed articles spanning the 2000–2024 period. GBA1-related PD has a worldwide distribution. It has long been recognized that pathogenic GBA1 mutations are particularly common in certain ethnic populations, including PD patients of Ashkenazi Jewish ancestry. Moreover, a considerable number of studies focused on European ancestry patients from Europe and North America have revealed a high proportion (up to 15%) of carriers among the PD population. GBA1 mutations also appear to play an important role in patient groups with an East Asian background, although the frequency of specific variants may differ as compared to those of European ancestry. Notably, the assessment of underrepresented populations in other parts of Asia (including India) and Latin America is in the spotlight of current research, while a variant with a newly described pathogenic mechanism has been reported in Sub-Saharan Africans. Given the importance of GBA1 mutations for PD genetics and clinical phenotype, a focused assessment of the prevalence and type of GBA1 variants in distinct ethnic populations will possibly inform ongoing PD-related clinical studies and facilitate upcoming therapeutic trials.