Exceptional Longevity and Polygenic Risk for Cardiovascular Health

Area of Science:

• Genetics
• Gerontology
• Cardiovascular Disease

Background:

• Exceptionally long-lived (ELL) individuals are key to understanding human longevity.
• Previous genetic studies suggest links between cardiovascular pathways, lipid, and cholesterol homeostasis with longevity.
• Polygenic risk scores (PRS) offer a way to assess genetic predisposition for complex traits.

Purpose of the Study:

• To investigate the genetic profiles of ELL individuals using polygenic risk scores (PRS).
• To determine if ELL individuals have a lower genetic predisposition for cardiovascular-related traits.
• To explore the association between genetic risk for exceptional longevity (EL) and longevity itself.

Main Methods:

• Assessed PRS in 294 ELL cases (95–106 years) and 1105 controls (55–65 years).
• Utilized genome-wide association study (GWAS) data with a p-value threshold of p < 5 × 10^-5.
• Constructed PRS from EL analyses and cardiovascular risk factors (lipids) and diseases (myocardial infarction, coronary artery disease, stroke).

Main Results:

• A higher genetic risk for exceptional longevity (EL) was significantly associated with longevity (OR = 1.19–1.20, p = 0.00804 and 0.00758).
• Two cardiovascular PRS (HDL cholesterol, triglycerides) were nominally significant with longevity but did not survive multiple testing correction.
• ELL individuals did not show significantly lower PRS for most investigated cardiovascular health traits.

Conclusions:

• The genetic predisposition for exceptional longevity is associated with longevity.
• ELL individuals do not exhibit a significantly lower polygenic risk for the majority of studied cardiovascular traits.
• Larger cohorts are needed to further elucidate the role of cardiovascular genetic variants in exceptional longevity.