Multi-ancestry population attributable risk assessment of common genetic variation in Alzheimer's and Parkinson's diseases
Jones, L.; Bandres Ciga, S.; Schumacher-Schuh, A. F.; Cerquera-Cleves, C.; Makarious, M. B.; Iwaki, H.; Nalls, M. A.; Noyce, A.; Global Parkinson's Genetic Program (GP2), ; Blauwendraat, C.; Singleton, A.; Mata, I.
Show abstract
Emerging evidence suggests that the genetic architecture of Alzheimers (AD) and Parkinsons diseases (PD) risk varies across ancestries. This study seeks to explore distinct and universal genetic targets across individuals of Latino, African/African Admixed, East Asian, and European populations by implementing Population Attributable Risk (PAR) comparisons on summary statistics from genome-wide association studies (GWAS). PAR was calculated for the most significant disease variants using summary statistics derived from select multi-ancestry GWAS meta-analyses, followed by fine-mapping analysis to validate genetic contribution of disease variants to European, African/African Admixed, East Asian, and Latino individuals. For both AD, APOE4 PAR estimates were universally high across all ancestries, with TSPAN14 and PICALM emerging as other common targets. Attributable risk varied across PD-related major risk loci including variation nearby GBA1 and LRRK2. In contrast, SNCA, MCCC1, VPS13C, and MAPT loci demonstrated comparable attributable risk across ancestries. This cross-ancestry evaluation of PAR reinforces the genetic heterogeneity of AD and PD. In consideration of the complex etiology of these diseases, these findings may inform the strategic prioritization of therapeutic targets and improve global health outcomes.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish 94%
- A Specialized Reference Panel with Structural Variants Integration for Improving Genotype Imputation in Alzheimer's Disease and Related Dementias (ADRD) 93%
- Accurate DNA Methylation Predictor for C9orf72 Repeat Expansion Alleles in the Pathogenic Range 92%
Similar papers in this journal
- The genetic overlap between Alzheimer’s disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease 96%
- Dissecting the role of Amerindian genetic ancestry and ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population 94%
- Mitochondrial pathway polygenic risk scores are associated with Alzheimer's Disease 94%