NIH Research Festival
FARE Award Winner
Aim: This research aims to conduct a comprehensive genome-wide study of Parkinson's disease (PD) in African and African admixed populations to elucidate ancestry-specific risk, genetic variations, and reveal novel disease mechanisms.
Background: Genetic understanding across varied populations can shed light on complex traits like PD. However, the majority of PD genetics knowledge comes from European, Asian, and Latin American populations, leaving a significant knowledge gap concerning African and African admixed ancestries.
Materials & Methods: We performed an extensive genome-wide assessment of PD in a large cohort comprising 197,918 individuals. The cohort included 1,488 PD cases and 196,430 controls, all of African and African admixed ancestry. Factors like ancestry-specific risk, differential haplotype structure, coding, structural genetic variation, and polygenic risk profiling were investigated.
Results: A novel PD risk factor at the GBA1 locus, specifically the intronic rs3115534-G variant, was discovered. This risk factor, influencing age at onset, is rare in non-African/African admixed populations. Unlike previous GBA1 associated risk variants, this new signal likely mediates PD risk via expression quantitative trait locus (eQTL) mechanisms, indicating a unique functional mechanism.
Discussion: This research identifies a novel GBA1 genetic risk factor in African and African admixed populations, contrasting prior studies on Northern European populations. The findings underscore the necessity for equitable inclusion in PD clinical trials, highlighting the importance of understanding ancestry-specific genetic risk. The inclusion of underrepresented groups offers fresh avenues towards RNA-based therapies aimed at reducing lifetime PD risk, crucial as the field progresses towards precision medicine in PD clinical trials.
Scientific Focus Area: Genetics and Genomics
This page was last updated on Monday, September 25, 2023