This repository contains data and code related to the study of Early-Onset Alzheimer's Disease (EOAD) in families enrolled in the Long Life Family Study (LLFS).
Background : LLFS families are known for their exceptional longevity and often live to old age without major chronic diseases (Wojczynski, 2022). Of the approximately 510 LLFS families from the US cohort:
3 families have been identified with familial EOAD (fEOAD).
42 families have sporadic EOAD cases.
The 3 familial EOAD families may represent a familial form of EOAD (fEOAD), which raises the hypothesis that there may be specific genetic variants that cause or influence EOAD within this population.
Research Aim : We aim to determine whether the 3 fEOAD families carry a Mendelian risk variant that causes EOAD. Since LLFS families were selected for their longevity and low prevalence of chronic disease, any causal variants identified in fEOAD families may reveal risk factors for EOAD. Furthermore, protective variants could also exist, potentially enabling family members to avoid or delay EOAD.
Hypothesis :
We reason that "The 3 fEOAD families are likely to carry a Mendelian risk variant that causes EOAD. If similar causal variants can be identified in other LLFS families who do not have EOAD, these individuals may carry protective variants that delay or prevent the onset of EOAD."
To identify and validate these potential risk and protective variants, we propose focusing on the following family types:
Sporadic EOAD Families : These families may have one individual affected by EOAD, while other family members either exhibit Late-Onset Alzheimer's Disease (LOAD) or are unaffected. The unaffected members may carry protective variants that have delayed EOAD onset.
LOAD Families : All members in these families may carry protective variants, making it a less likely group for initial candidate analysis but still relevant for broader studies on longevity and Alzheimer's risk reduction. This repository contains scripts and analysis code for identifying and analyzing potential causal and protective variants in LLFS family members with EOAD. Please refer to the documentation for further details on usage and data processing steps.
Contact: For questions, reach out via the Issues page, or email [email protected].