Population Attributable Risk in Alzheimer and Parkinson Diseases.
Population Attributable Risk in Alzheimer and Parkinson Diseases.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Bogotá, CO · Author affiliation
Department of Neurosciences, Neurology Unit, Hospital Universitario San Ignacio, Bogotá, Colombia;Location evidence
Laval, CA · Author affiliation
CHU de Québec Research Center, Axe Neurosciences, Université Laval, Quebec City, Canada;Location evidence
Québec, CA · Author affiliation
CHU de Québec Research Center, Axe Neurosciences, Université Laval, Quebec City, Canada;Location evidence
Rio Grande, BR · Author affiliation
Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;Location evidence
Porto Alegre, BR · Author affiliation
Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;Location evidence
London, GB · Author affiliation
Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, United Kingdom;Location evidence
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Original abstract
OBJECTIVES: Emerging evidence suggests that the genetic architecture of Alzheimer disease (AD) and Parkinson disease (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 using summary statistics from genome-wide association studies (GWASs). METHODS: 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. RESULTS: For 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. By contrast, SNCA, MCCC1, VPS13C, and MAPT loci demonstrated comparable attributable risk across ancestries. DISCUSSION: 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.