Dissecting Alzheimer's disease heritability across populations

Area of Science:

• Genetics
• Neuroscience
• Epidemiology

Background:

• Late-onset Alzheimer's disease (LOAD) is a significant public health concern.
• LOAD exhibits high heritability, but precise estimates across different populations are not well-established.

Purpose of the Study:

• To estimate the family-based heritability of LOAD across diverse ancestral populations.
• To investigate the influence of age, sex, APOE ε4, and study population on LOAD heritability.

Main Methods:

• Utilized Alzheimer's Disease Sequencing Project (ADSP) pedigrees from non-Hispanic White, non-Hispanic Black, Dominican, and Dutch isolate populations.
• Employed two statistical methods: Statistical Analysis for Genetic Epidemiology (S.A.G.E.) and Sequential Oligogenic Linkage Analysis Routines (SOLAR-Eclipse).
• Incorporated models adjusting for age, sex, apolipoprotein E ε4 (APOE ε4), and study-specific effects.

Main Results:

• Heritability estimates for LOAD varied substantially by population and analytical method.
• S.A.G.E. estimates ranged from 29.1% (non-Hispanic White) to 78.3% (Dutch isolate), while SOLAR-Eclipse estimates ranged from 45.2% to 80.2%.
• APOE ε4 adjustment reduced heritability estimates by approximately 4.9% on average.

Conclusions:

• LOAD heritability is population-dependent, suggesting potential variations in genetic risk factors or environmental influences across groups.
• Findings highlight the importance of considering population-specific genetic architectures in LOAD research.