Key takeaway: Absence of CAD disease risk alleles is one key-feature linked to longevity and alleles linked to cholesterol metabolism are a key component in healthy aging trajectories.
@jorisdeelen.bsky.social @marianbeekman.bsky.social

Finally, we constructed a novel cholesterol-metabolism-PGS, based on gene-annotation enrichment analysis, that predicted time to all-cause mortality in two independent 90+ study populations.

Using accelerated failure time modelling, we further showed that a lower PGS for CAD explains up to 20% of the delay in cardiovascular disease incidence in descendants of long-lived families.

We showed that having an increasing number of long-lived ancestors is additively associated with lower genetic risk for coronary artery disease (CAD).

We investigated this hypothesis in the Leiden Longevity Study, a cohort with data from more than 400 long-lived families in 3-generations and the Leiden 85+ study. To analyze our data, we constructed a set of polygenic scores (PGS) covering the top diseases causing most deaths in the Netherlands.

We hypothesize that one of the key features explaining healthy survival up to high ages (longevity) is the absence of chronic disease risk alleles.

To address this question, we examined descendants of long-lived families who maintain exceptional health as they age and show a delay of more than ten years in the onset of chronic diseases.