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Basic Science and Pathogenesis.

Shiying Liu1, William S Bush2, Brian W Kunkle3

  • 1Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.

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Summary
This summary is machine-generated.

Heritability of late-onset Alzheimer disease (LOAD) varies significantly across populations. Genetic and environmental factors contribute to these differences, highlighting the need for diverse population studies in LOAD research.

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Area of Science:

  • Genetics
  • Neuroscience
  • Population Health

Background:

  • Late-onset Alzheimer disease (LOAD) exhibits high heritability, estimated up to 80% in European populations.
  • Previous studies have not fully explored the range of LOAD heritability across diverse populations.
  • The influence of factors like APOE, race/ethnicity, and cohort effects on LOAD heritability is not well understood.

Purpose of the Study:

  • To estimate family-based heritability of LOAD across diverse racial and ethnic groups.
  • To investigate the impact of APOE ε4 carrier status and cohort effects on heritability estimates.
  • To compare heritability estimates derived from different statistical methods (S.A.G.E. and SOLAR).

Main Methods:

  • Utilized Alzheimer's Disease Sequencing Project (ADSP) pedigrees and genome-wide data from five racial/ethnic groups.
  • Calculated family-based heritability using S.A.G.E. and SOLAR, adjusting for age, sex, APOE ε4 status, and cohort.
  • Analyzed data from non-Hispanic White, non-Hispanic Black, Dominican, Puerto Rican, and Dutch Isolate populations.

Main Results:

  • Heritability estimates for LOAD showed significant variability across populations, regardless of the method or adjustments used.
  • Estimates were highest in Dutch isolates (78.3%) and lowest in non-Hispanic Whites (29.1%) using S.A.G.E. (model 1).
  • APOE ε4 carrier status and cohort adjustments had a modest impact on heritability estimates, with SOLAR generally yielding higher estimates than S.A.G.E.

Conclusions:

  • The wide range of heritability estimates underscores the importance of population-specific genetic and unmeasured environmental factors in LOAD.
  • Findings complement twin-based and genome-wide studies, emphasizing the need for diverse cohorts.
  • Ongoing research aims to compare SNP-based heritability with family-based estimates for a comprehensive understanding.