Category: Parkinson's Disease: Genetics
Objective: To explore the genetic architecture of Parkinson’s disease (PD) in Egypt, addressing the underrepresentation of this population in PD genetics research.
Background: Genetic studies lack diversity, with over 80% of genome-wide association studies (GWAS) conducted on individuals of European ancestry. In PD research, many Mideastern and African populations remain underrepresented. The GP2 Underrepresented Populations Working Group and iPDGC Africa aim to address this disparity. The latter initiative, a collaboration between GP2 and institutions in five African countries, includes our Egyptian research group.
Method: Genotyping was performed using Neurobooster Illumina arrays, with rigorous quality control applied at both array and variant levels. The final cohort comprised 293 PD patients and 358 healthy controls. We screened for rare PD-associated pathogenic variants (MAF <0.05) in cases versus controls. Heritability was estimated using genome-based restricted maximum likelihood (GREML) in genome-wide complex trait analysis (GCTA), leveraging genetic-relatedness matrices from genome-wide SNP data. Copy number variation (CNV) analysis was conducted using the PennCNV calling pipeline.
Results: Screening for known rare mutations in PD-associated genes identified variants in PINK1, GIGYF2, PLA2G6, GBA1, ATP1A3, LRRK2, and ADH1C, suggesting these genes may contribute to PD susceptibility in the Egyptian population. CNV analysis revealed a PD-specific duplication in 1p36.33-q44, spanning PD-associated risk genes (DJ1, VPS13D, ATP13A2, PINK1, DNAJC6). Additional duplications were observed in 1q21.3 and 2q37.3, involving DNAJC6 and SLC19A3, respectively. Heritability analysis estimated PD heritability at 47.78%, though not statistically significant, suggesting that genetic variance alone may not be a primary determinant of PD phenotype in this cohort.
Conclusion: This pilot study offers novel insights into the genetic architecture of PD in Egypt, highlighting potential population-specific genetic contributions. While these findings require validation in larger studies, they contribute to reducing disparities in global PD genetics research.
To cite this abstract in AMA style:
M. Yousef, A. El-Hosseiny, A. Nagano, A. Atputhavadivel, E. Khedr, M. William, A. Shalash, G. Fawy, S. El-Shafie, S. El-Jaafary, M. Koraym, Y. Salah, S. Elfarrash, Y. Elsaid, A. Gabr, N. Shebl, L. Aly, N. Abdelwahhab, T. Belal, N. Elsayed, M. El-Gamal, S. Elgamal, S. Ragab, J. Mekky, M. Salama, M. Rizig. Rare Variants, Copy Number Variations, and Heritability Estimates in a Pilot Cohort of Egyptians with Parkinson’s Disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/rare-variants-copy-number-variations-and-heritability-estimates-in-a-pilot-cohort-of-egyptians-with-parkinsons-disease/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/rare-variants-copy-number-variations-and-heritability-estimates-in-a-pilot-cohort-of-egyptians-with-parkinsons-disease/