Rare longevity-associated variants, including a reduced-function mutation in cGAS, identified in multigenerational long-lived families.

ABSTRACT: Life expectancy has steadily increased in the last two centuries, while healthspan has been lagging behind. Survival into extreme ages strongly clusters within families which often exhibit a delayed onset of (multi)morbidity, yet the underlying protective genetic mechanisms are still largely undefined. We performed affected sib-pair linkage analysis in 212 sibships enriched for ancestral longevity and identified four genomic regions (LOD_max ≥3.0) at 1q21.1, 6p24.3, 6q14.3, and 19p13.3. Within these regions, we prioritized 12 rare protein-altering variants in seven candidate genes (NUP210L, SLC27A3, CD1A, CGAS, IBTK, RARS2, and SH2D3A) located in longevity-associated loci. Notably, a missense variant in CGAS (rs200818241), was pres

SUBMITTER: Putter PC 

PROVIDER: S-EPMC12713140 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature