LIMITATIONS OF POLYGENIC RISK SCORES FOR DEMENTIA IN FAMILIAL EXCEPTIONAL AGING: IMPACT OF SAMPLING
2024

Limitations of Genetic Risk Scores for Dementia in Long-Lived Individuals

publication Evidence: moderate

Author Information

Author(s): Xicota Laura, Cheng Rong, Rodriguez Sandra Barral, Honig Lawrence, Lee Joseph

Primary Institution: Columbia University

Hypothesis

Do genetic risk factors for late-onset Alzheimer's disease impact AD risk in exceptionally long-lived individuals?

Conclusion

Genetic risk factors for Alzheimer's disease identified in the general population do not predict AD risk in a cohort of long-lived individuals.

Supporting Evidence

  • PRS based on two large GWASs in the general population did not predict clinical AD status in the LLFS population.
  • Only 6.7% of SNPs from GWAS 1 and 7.7% from GWAS 2 were associated with AD.
  • Levels of AD biomarkers were not positively associated with PRS.

Takeaway

This study found that the genetic markers used to predict Alzheimer's risk in most people don't work the same way for people who live a very long time.

Methodology

The study examined the relationship between polygenic risk scores and Alzheimer's disease biomarkers in a cohort of long-lived individuals.

Limitations

The study is limited to US sites and may not generalize to other populations.

Participant Demographics

Participants were exceptionally long-lived individuals from the Long Life Family Study.

Digital Object Identifier (DOI)

10.1093/geroni/igae098.0028

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